MOLECULAR MACHINES STIMULATE INTERCELLULAR CALCIUM WAVES AND CAUSE MUSCLE CONTRACTION This application claims the benefit of priority to United States Provisional Application No. 63/421,033, filed on October 31, 2022, the entire contents of which are hereby incorporated by reference. BACKGROUND 1. Field This disclosure relates to the fields of biology, biochemistry, chemistry, pharmacology and medicine. In particular, new methods related to calcium signaling and muscle contraction are disclosed. 2. Related Art Neurological disorders frequently have severe and long-term adverse effects on physical well- being and quality of life. In many patients these disorders cause significant disability, and in some cases, they may be life-threatening. For example, Alzheimer’s disease, Parkinson’s disease, schitzophrenia and Huntington’s disease affect a large percentage of the population, yet there is a significant lack of viable treatments for these disorders. Calcium signaling dysregulation is a common feature of neurological disorders, as abnormal signaling patterns have been shown to cause mitochondrial dysfunction and synaptic instability (Pschitskaya, et al.). Therefore, the regulation of calcium signaling pathways represents a significant and urgent unmet medical need for use in the treatment of neurological and neuro-related disorders. In single cells, calcium directly controls many different processes, including cellular proliferation, gene expression, and movement (Tsutsumi et al., Screaton et al., Carrasco & Hidalgo, and Schmid & Salathe). In vitro, cells also utilize calcium to control their communication with surrounding cells. These signals propagate into waves via the diffusion of secondary messengers, and these waves are used to coordinate the action of large groups of cells, tissues, or organs. In organisms, calcium signals can propagate through secondary messengers to cause intercellular calcium waves (ICW) that coordinate concerted action in whole tissues (McCormack et al.). ICWs are triggered by a variety of stimuli and involve the release of Ca ²⁺ from internal stores (Leybaert & Sanderson). The propagation of ICWs predominately involves cell communication with internal messengers moving via gap junctions or extracellular messengers mediating paracrine signaling. The speed and size of ICWs depend on the nature and strength of the initiating stimulus as well as the mechanism of propagation. Previous work involving ICWs has been conducted using membrane-targeted molecular photoswitches to modulate neuronal activity (DiFrancesco et al.). This approach involves the mechanical modulation of membrane thickness via reversible switching, a distinct approach to a machine that possesses separate advantages and drawbacks compared to the present technique. Molecular switches differ from motors in that they do not rotate unidirectionally and thus do not perform mechanical work. Previous work (Garcia-Lopez et al.) has also shown that unidirectional rotation is necessary to drill holes in lipid bilayers, distinguishing their bioactivity. Consequentially, motors apply more mechanical force than switches, which is why the switches in DiFrancesco et al. had to be targeted to the cell membrane to affect neuronal excitability. Second, while the ICWs driven by molecular machines (MM) may be used to affect neuronal excitability, this only occurs as a downstream consequence of ICWs. No previous work has used either a machine or a switch to cause ICWs. Hence, while direct neuronal stimulation via membrane thinning may be desirable in some instances (i.e. rapidly triggering specific targeted neurons), ICWs driven by MM may be advantageous in others (i.e. stimulating networks of neurons or glia). There is also a growing need to interface with biological systems at the molecular level (Zhu et al.,2020). Accompanied by that demand, the challenge that most therapeutic methods are difficult to target to specific tissues is taken more and more seriously. Treating disease with better spatiotemporal resolution is appreciated and can be achieved by using light-activated therapeutics, which can be controlled in terms of the duration, location, and magnitude of stimulation (Chen et al.,2020). The use of light to control molecular scale cellular processes would be advantageous in both the scientific study and treatment of many types of disease. Light-based techniques to treat disease would be particularly beneficial in the field of skeletal muscle contraction, enabling essential functions such as movement, posture, and respiration (McCuller et al.,2023). Dysfunction or loss of skeletal muscle function due to trauma, neuromuscular disorders, or age-related degeneration, severely impact a patient’s quality of life (Wilkinson et al.,2018). Consequently, there is a growing need for innovative approaches to stimulate skeletal muscle contraction, both as a research tool and as a potential therapeutic intervention. Current techniques for stimulating muscle contraction use either drugs or electrical stimulation (Kaji et al.,2010), which lack precision and selectivity. The development of light-based techniques with better spatiotemporal resolution to induce muscle contraction at the cellular level may contribute to the development of effective strategies to restore muscle function and improve the lives of individuals affected by muscle- related disorders. A recent and unique approach to influence biological activity at the molecular level is using light-activated molecular motors (MMs) (Beckham et al.,2023; Santos et al.,2022; Santos et al.,2023; García-López et al.,2017; Ayala Orozco et al.,2020; Guinart et al, 2023). MMs are molecules capable of exerting work on their surroundings through mechanical force (Browne and Feringa, 2006; Erbas- Cakmak et al.,2015; Aprahamian, 2020; Eelkema et al.,2006) and have recently been used to mechanically influence cellular processes (Watson and Cockroft, 2016; Zheng et al.,2021). Recent work done by Beckham et al.6 showed the ability of MMs to initiate cellular calcium signaling when irradiated with light. This signaling occurred by means of the inositol triphosphate (IP ₃ ) pathway and was shown to induce contraction in vitro in cardiomyocytes and in vivo in Hydra vulgaris. Their work demonstrated how MMs could be used to directly control cell signaling and downstream biological function in those specific cell types. A common model for studying skeletal muscle contraction in vitro is C2C12 myoblast, an immortalized mouse skeletal cell line (Kaju et al.,2010; Yaffe and Saxel, 1977). Myoblasts are initially plated in cell culture dishes and are akin to satellite muscle cells in vivo. Upon reaching confluency, C2C12 myoblasts will differentiate into multinucleated myotubes, much like how satellite cells in vivo fuse to form muscle fibers. C2C12 myotubes are contractile and suitable for studying muscle cell contraction in vitro (Dennis et al.,2001). Studying these contractions in vitro increases our knowledge of how muscle contraction and related diseases occur in vivo and eventually leads to better treatment of these diseases in humans. In particular, in vitro models like C2C12 myotubes are important for studying how muscle contraction can be initiated at the molecular level because experiments can be done on individual cells and avoid the ethical challenges of experimenting on animals. Other methods using MM have explored targeted receptor-machine binding as a way to exert mechanical force on distinct ion channels (Zheng et al.). The technique described herein does not require an antibody as the MM are able to elicit calcium signaling directly. This results in significantly greater response magnitude in single cells. Furthermore, this technique differs mechanistically in that MM are used to interact with membrane signaling and not intracellular signaling. However, an ICW was not elicited during this interaction, and to date, there has been no reported method of MM-induced muscle contraction or ICWs. Overall, there remains a need to find new and unique ways to control calcium signaling pathways using MM to generate ICWs, and consequently improve treatment for neurological and neuro- related disorders. SUMMARY As provided herein, the present disclosure relates to methods of regulating calcium signaling pathways using ICWs. In some aspects, the present disclosure provides a method of inducing an intercellular calcium wave (ICW), the method comprising: (A) contacting a stimulus-responsive molecular machine or switch with a cell, tissue or organism; and (B) activating the molecular machine or switch using a stimulus to induce an ICW. In other aspects, the present disclosure provides a method of modulating calcium signaling comprising: (A) contacting a stimulus-responsive molecular machine or switch with a cell, tissue or organism; and (B) activating the molecular machine or switch using a stimulus causing the cell, tissue, or organism to release calcium ions. In other aspects, the present disclosure provides a method of stimulating neural activity, the method comprising: (A) contacting a stimulus responsive molecular machine or switch with a cell, tissue or organism; and (B) activating the molecular machine or switch to induce neural activity. In other aspects, the present disclosure provides a method of stimulating a muscle contraction, the method comprising: (A) contacting a stimulus responsive molecular machine or switch with a muscle cell; and (B) activating the molecular machine or switch to induce a muscle contraction. In other aspects, the present disclosure provides a method of treating a disease or disorder associated with calcium ion misregulation comprising: (A) administering to a patient in need thereof a stimulus responsive molecular machine or switch; and (B) exposing the stimulus responsive molecular machine to a stimulus to facilitate the release of calcium ions. In some embodiments, the molecular machine comprises a Feringa-type, a hemithioindigo- type, or molecular machine activated by a vibronic mode. In some embodiments, the molecular machine or switch comprises a rotor that is connected to a stator. In some embodiments, the molecular machine or switch comprises a rotor that is connected to a stator through an alkenyl or alkynyl group such as an atropisomeric alkene. In some embodiments, the rotor comprises one, two, three, four, or five rings such as one, two, or three aromatic rings. In some embodiments, the rotor comprises one, two, or three aliphatic rings. In some embodiments, the rotor comprises one, two, or three aromatic rings and one or two aliphatic rings. In some embodiments, the rotor comprises one, two, or three aliphatic or aromatic rings such as two aromatic rings and an aliphatic ring. In some embodiments, the rotor is further defined as: wherein: R1 and R1ƍ^DUH^HDFK^independently hydrogen, a C1-C12 alkyl or a C1-C12 substituted alkyl; R ₂ is hydrogen, amino, cyano, halo, hydroxy, C1-C12 alkyl, C3-C12 cycloalkyl, C1-C12 alkenyl, C1-C12 alkynyl, C1-C12 aryl C1-C12 aralkyl, C1-C12 heteroaryl, C1-C12 heteroaralkyl, C1-C12 heterocycloalkyl, C1-C12 alkoxy, C1-C12 alkylamino, C1-C12 dialkylamino, C1-C12 acyl, C1-C12 amido, C1-C12 acyloxy, or a substituted version of any of these groups; or R ₂ is a group of the formula^^í< ₁ íX ₁ íR ₂ ƍ^^ZKHUHLQ^ Y ₁ LV^í2í^^í6í^^RU^í15 _a í, wherein: R _a is hydrogen, C1-C6 alkyl, or substituted C1- C6 alkyl; X ₁ is C1-C12 alkanediyl, C1-C12 substituted alkanediyl, C3-C12 cycloalkanediyl, C3- C12 substituted cycloalkanediyl, C6-C12 arenediyl, and C6-C12 substituted arenediyl; and R2ƍ^LV^í15bRbƍ^^ZKHUHLQ^5b and Rbƍ^DUH^each independently hydrogen, C1-C6 alkyl, or C1-C6 substituted alkyl; and n is 0, 1, 2, 3, or 4. In some embodiments, the rotor is further defined as: wherein: R ₂ is hydrogen, amino, cyano, halo, hydroxy, C1-C12 alkyl, C3-C12 cycloalkyl, C1-C12 alkenyl, C1-C12 alkynyl, C1-C12 aryl, C1-C12 aralkyl, C1-C12 heteroaryl, C1-C12 heteroaralkyl, C1-C12 heterocycloalkyl, C1-C12 alkoxy, C1-C12 alkylamino, C1-C12 dialkylamino, C1-C12 acyl, C1-C12 amido, C1-C12 acyloxy, or a substituted version of any of these groups; or R2 LV^D^JURXS^RI^WKH^IRUPXOD^^í<1íX1íR2ƍ^^ZKHUHLQ^ Y1 LV^í2í^^í6í^^RU^í15aí, wherein: Ra is hydrogen, C1-C6 alkyl, or substituted C1- C6 alkyl; X1 is C1-C12 alkanediyl, C1-C12 substituted alkanediyl, C3-C12 cycloalkanediyl, C3- C12 substituted cycloalkanediyl, C6-C12 arenediyl, and C6-C12 substituted arenediyl; and R2ƍ^LV^í15bRbƍ^^ZKHUHLQ^5b and Rbƍ^DUH^HDFK^LQGHSHQGHQWO\^K\GURJHQ^^&^-C6 alkyl, or C1-C6 substituted alkyl; and n is 0, 1, 2, 3, or 4. In some embodiments, R ₁ is C1-C12 alkyl or substituted C1-C12 alkyl. In some embodiments, R ₁ is C1-C12 alkyl, such as methyl. In some embodiments, R ₁ ƍ^LV^K\GURJHQ^ In some embodiments, R ₂ is hydrogen. In some embodiments, R ₂ is íY ₁ íX ₁ íR ₂ ƍ^ In some embodiments, Y ₁ LV^í15 _a í. In some embodiments, R _a is hydrogen. In some embodiments, X ₁ is C1-C12 alkanediyl or C1-C12 substituted alkanediyl, such as C1-C12 alkanediyl. In some embodiments, X ₁ is etheylene. In some embodiments, R _b is C1-C6 alkyl or C1-C6 substituted alkyl. In some embodiments, R _b is C1-C6 alkyl, such as methyl. In some embodiments, R _b ƍ^LV^&^-C6 alkyl or C1-C6 substituted alkyl. In some embodiments, R _b ƍ^LV^&^- C6 alkyl, such as methyl. In some embodiments, R ₂ LV^í1+&+ ₂ CH ₂ N(Me) ₂ . In some embodiments, n is 0. In other embodiments, n is 1. In some embodiments, the stator comprises one, two, three, four, or five rings, such as one, two, three, four, or five aromatic rings. In some embodiments, the stator comprises one, two, or three aromatic rings. In some embodiments, the stator comprises one, two, three, four, or five aliphatic rings. In some embodiments, the stator comprises one, two, or three aliphatic rings. In some embodiments, the stator comprises two, three, or four rings. In some embodiments, the stator comprises three rings. In some embodiments, the stator comprises three rings with at least 2 aromatic rings. In some embodiments, the stator is further defined as: wherein: X ₂ is a covalent bond, O, S, NR _c , or CR _d R _d ƍ^^ZKHUHLQ^5 _c , R _d , and R _d ƍ^DUH each independently hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl; R ₃ is hydrogen, amino, cyano, halo, hydroxy, C1-C12 alkyl, C3-C12 cycloalkyl, C1-C12 alkenyl, C1-C12 alkynyl, C1-C12 aryl, C1-C12 aralkyl, C1-C12 heteroaryl, C1-C12 heteroaralkyl, C1-C12 heterocycloalkyl, C1-C12 alkoxy, C1-C12 alkylamino, C1-C12 dialkylamino, C1-C12 acyl, C1-C12 amido, C1-C12 acyloxy, or a substituted version of any of these groups; or R ₃ is a group of the formula^^í< ₂ íX ₃ íR ₃ ƍ^^ZKHUHLQ^ Y ₂ LV^í2í^^í6í^^RU^í15 _e í, wherein: R _e is hydrogen, C1-C6 alkyl, or substituted C1- C6 alkyl; X ₃ is C1-C12 alkanedyl, C1-C12 substituted alkanediyl, C3-C12 cycloalkanediyl, C3-C12 substituted cycloalkanediyl, C6-C12 arenediyl, and C6-C12 substituted arenediyl; and R3ƍ^LV^í15fRfƍ^^wherein Rf and Rfƍ^DUH^HDFK^LQGHSHQGHQWO\^K\GURJHQ^^&^-C6 alkyl, or C1-C6 substituted alkyl; and m is 0, 1, 2, 3, or 4. In some embodiments, the stator is further defined as: wherein: X2 is a covalent bond, O, S, NRc, or CRdRdƍ^^ZKHUHLQ^5c, Rd, and Rdƍ^DUH^HDFK^LQGHSHQGHQWO\^ hydrogen, C1-C6 alkyl, or substituted C1-C6 alkyl. In some embodiments, R3 is íY2íX3íR3ƍ. In some embodiments, Y2 LV^ í15eí. In some embodiments, Re is hydrogen. In some embodiments, X3 is C1-C12 alkanediyl or C1-C12 substituted alkanediyl, such as C1-C12 alkanediyl. In some embodiments, X3 is etheylene. In some embodiments, Rf is C1-C6 alkyl or C1-C6 substituted alkyl. In some embodiments, Rf is C1-C6 alkyl, such as methyl. In some embodiments, Rfƍ^LV^&^-C6 alkyl or C1-C6 substituted alkyl. In some embodiments, Rfƍ^LV^&^- C6 alkyl, such as methyl. In some embodiments, R2 LV^í1+&+2CH2N(Me)2. In some embodiments, n is 0. In other embodiments, n is 1. In some embodiments, X2 is S. In other embodiments, X2 is a covalent bond. In some embodiments, X2 is CRdRdƍ^ In some embodiments, Rd is C1-C6 alkyl or C1-C6 substituted alkyl. In some embodiments, Rd is C1-C6 alkyl, such as methyl. In some embodiments, Rdƍ^ is C1-C6 alkyl or C1-C6 substituted alkyl. In some embodiments, Rdƍ is C1-C6 alkyl, such as methyl. In some embodiments, the molecular machine or switch is further defined as: . In some embodiments, the molecular machine or switch rotates unidirectionally. In other embodiments, the molecular machine or switch rotates bidirectionally. In some embodiments, the rotational component of the molecular machine or switch rotates at a speed greater than 1 Hz. In some embodiments, the rotational component of the molecular machine or switch rotates at a speed greater than 10 ⁵ Hz. In some embodiments, the rotational component of the molecular machine or switch rotates at a speed of about 10 ⁶ Hz. In other embodiments, the rotational component of the molecular machine or switch rotates at a speed of about 10 ⁸ Hz. In some embodiments, the molecular machine or switch is activated by electromagnetic radiation, such as gamma rays, X-rays, UV light, visible light, near infrared light, infrared light, microwaves, or radio waves. In some embodiments, the electromagnetic radiation comprises UV light, visible light, or near infrared light. In some embodiments, the electromagnetic radiation comprises visible light. In some embodiments, the electromagnetic radiation comprises a wavelength of 400 nm or 405 nm. In some embodiments, the molecular machine or switch is activated for a controlled time period. In some embodiments, the molecular machine or switch is activated for less than 5 seconds. In some embodiments, the molecular machine or switch is activated for less than 2 seconds. In some embodiments, the molecular machine or switch is activated for about 250 milliseconds. In some embodiments, the energy source is a laser. In other embodiments, the energy source is a light-emmitting diode (LED). In some embodiments, the intensity of the energy source is controlled. In some embodiments, the method results in the control of a calcium-driven process. In some embodiments, the calcium-driven process is controlling muscle contraction, neuronal firing, blood vessel dilation, digestion, tissue differentiation or ATP production. In some embodiments, the method is used to regulate behavioral patterns. In some embodiments, the method is used to regulate organ development, blood vessel dilation, heart contraction, brain activity, optical activity, auditory activity, and hormone secretion. In some embodiments, the method comprises contacting a cell. In some embodiments, the cell is a muscle cell. In other embodiments, the cell is a glial cell. In other embodiments, the cell is a heart cell. In some embodiments, the method comprises contacting an organism. In some embodiments, the organism is an invertebrate. In some embodiments, the subject is a mammal. In some embodiments, the disease or disorder is a neurodegenerative disease, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, or Huntington’s disease. In some embodiments, the disease or disorder is a neuropsychiatric disorder, such as schizophrenia, depression, bipolar disorder, epilepsy, post-traumatic stress disorder, attention deficit disorder, autism, or anorexia nervosa. In some embodiments, the disease or disorder is associated with mitochondrial dysfunction. In some embodiments, the disease or disorder is a cancer, such as chordoma, medulloblastoma, neuroblastoma meningioma, pituitary adenoma, craniopharyngioma, schwannoma, nasopharyngeal angiofibroma, neurofibroma, hemangioblastoma or osteoma. In some embodiments, the disease or disorder is a heart disease. In some embodiments, the disease or disorder is a motor disease, such as amyotrophic lateral sclerosis, progressive bulbar palsy, primary lateral sclerosis, progressive muscular atrophy, spinal muscular atrophy, Kennedy's disease, or post-polio syndrome. In some embodiments, the method comprises contacting the cell, tissue, or organism with the molecular machine once. In other embodiments, the method comprises contacting the cell, tissue, or organism with the molecular machine two or more times. In some embodiments, the method comprises contacting the cell, tissue, or organism with the molecular machine that is bound to a targeting group such as a petide or antibody. It is contemplated that any method described herein can be implemented with respect to any other method described herein. Other objects, features and advantages of the present disclosure will become apparent from the following detailed description. It should be understood, however, that the detailed description and the specific examples, while indicating specific embodiments of the disclosure, are given by way of illustration only, since various changes and modifications within the spirit and scope of the disclosure will become apparent to those skilled in the art from this detailed description. BRIEF DESCRIPTION OF THE DRAWINGS The following drawings form part of the present specification and are included to further demonstrate certain aspects of the present invention. The invention may be better understood by reference to one or more of these drawings in combination with the detailed description of specific embodiments presented herein. FIG 1A-D - Structures of MM used herein, their mechanism of rotation, and their activation to induce ICW in HEK293 cells. (a) The rotation cycle of a typical MM, showing two photoisomerizations (hQ^^DQG^WZR^WKHUPDO^^ǻ^^KHOL[^LQYHUVLRQV^WR^FRPSOHWH^D^XQL GLUHFWLRQDO^URWDWLRQ^^^7KH^PRLHW\^LQ^WKH^³;´^ position can be changed to synthesize MM of different rotation speeds. (b) Structures of the MM employed in this study. MM 1 and MM 2 complete fast (MHz-scale) unidirectional rotation. MM 3 rotates at 0.1 Hz at room temperature. MM 4 lacks chirality imparted by the allylic methyl and possesses no preference for unidirectional rotation. (c) Confocal microscope images of cells treated with MM 1, calcium-tracking dye Fluo-4, and cell membrane labeling dye CellMask (used to differentiate individual cells), showing a rapid increase in intracellular calcium levels after stimulation with 400 nm light. The red dotted circle labels the area of laser stimulation. The images in the top row were taken before stimulation, and the images in the bottom row were taken immediately prior to, 1 s after, and 2 min after stimulation. The scale bar applies to all images and is 20 µm. (d) Representative normalized fluorescence intensity traces of Fluo-4 in HEK293 cells treated with each MM. The solid line represents the average responses of n=6 independent cells, and the shaded area represents the standard error of the mean. MM 1, MM 2, and MM 4 were administered to cells at 8 µM. MM 3 was administered to cells at 24 µM. Stimuli for cells treated with MM 1, 2, and 4 used a 250 ms pulse width delivered to a circular area of diameter 5 µm at 3.2×10 ² W cm ^-2 . Stimuli for cells treated with MM 3 were administered at 6.4×10 ² W cm ^-2 . For all plots, the cyan line indicates the time of stimulus presentation. FIG.2 – Comparison to vehicle control. Normalized fluorescence intensity traces of Fluo-4 in HEK293 cells treated with either MM 1 (8 µM) or DMSO vehicle (0.1% v/v). The solid lines represent the average of n=6 cells. The shaded area represents the standard error of the mean. FIG. 3 – MM-induced ICW propagate according to the degree of electrical connection in stimulated tissue. Fluo-4 fluorescence traces of HEK293 cells treated with MM 1 from a single colony (corresponding to FIGS.38A-D), showing propagation of signal to surrounding cells over the timespan RI^VHYHUDO^PLQXWHV^^7KH^FHOO^PDUNHG^³^´^ZDV^VWLPXODWHG^ZLW K^D^^^^^PV^SXOVH^RI^^^^^QP^OLJKW^GHOLYHUHG^ to a 5 µm diameter circular region of interest at 3.2×10 ² W cm ^-2 . The image on the left shows the cells from which the traces are derived. The numbers on each individual cell denote the separation, in number of cells, from the stimulated cell. The plot on the right shows normalized intensity traces of both the VWLPXODWHG^FHOO^DQG^WKH^RWKHU^FHOOV^LQ^WKH^FRORQ\^^7KH^FHOOV ^PDUNHG^³^ ^st CRQQ´^ZHUH^GLUHFWO\^FRQQHFWHG^ WR^WKH^VWLPXODWHG^FHOO^DQG^FRUUHVSRQG^WR^WKH^FHOOV^PDUNHG^³ ^´^LQ^WKH^OHIW^LPDJH^^7KH^FHOOV^PDUNHG^³^ ^nd &RQQ´^ZHUH^FRQQHFWHG^WR^D^FHOO^GHVLJQDWHG^³^ ^st &RQQ´^DQG^FRUUHVSRQG^WR^FHOOV^PDUNHG^³^´^LQ^WKH^OHIW^ LPDJH^^7KH^FHOO^PDUNHG^³3 ^rd &RQQ´^ZHUH^FRQQHFWHG^WR^FHOOV^GHVLJQDWHG^³^ ^nd &RQQ´^DQG^FRUUHVSRQG^WR^ WKH^FHOOV^PDUNHG^³^´^LQ^WKH^OHIW^LPDJH^^6FDOH^EDU^LV^^^^^P ^ FIGS. 4A-4C – Administration of ROS scavengers does not affect MM induced ICW. Normalized fluorescence intensity traces of HEK293 cells treated with MM 1 and Fluo-4 and administered (a) melatonin (Mel; 100 µM), (b) thiourea (ThioU; 50 mM), and (c) L-ascorbic acid (Vit C; 2 mM). The shaded region indicates the standard error of n=6 stimulation attempts. Dark traces indicate positive controls collected prior to treatment. Stimulation was administered at 4.5×10 ² W cm- ² . Cells were incubated with chosen ROS scavengers for 1 h prior to stimulation. FIG. 5 – Normalized fluorescence intensity traces of X-Rhod-1 in HEK293 cells treated with MM 1 and stimulated with a 250 ms pulse of 400 nm light delivered to a 5 µm diameter circular region of interest at 3.2×10 ² W cm ^-2 . Different colors represent distinct cells. X-Rhod-1 was loaded into cells at 2 µM over a period of 45 min and excited using 561 nm laser light in a Nikon A1 Rsi fluorescence microscope. FIGS.6A & 6B – Calcium responses to MM are repeatable. (a) Fluorescence traces of Fluo-4 in HEK293 cells treated with MM 1 as described in the Methods section and stimulated multiple times (3.2×10 ² W cm ^-2 ^^^^^P^GLDPHWHU^^^^^^PV^SXOVH^WLPH^^^7KH^³QHJDWLYH^FR QWURO´^UHSUHVHQWV^YHKLFOH-treated (0.1% DMSO) cells that were subjected to the same irradiation regime as MM-treated cells. The shaded region represents the standard error of the mean across n=6 cells. (b) Magnitude of changes in intracellular calcium levels in MM 1-treated cells exposed to multiple light stimulations. Error bars represent the standard error of n=6 cells. The cyan line indicates the time of stimulus presentation. FIGS. 7A & 7B – Light power dependence of the responses of HEK293 cells to MM 1. (a) Representative fluorescent intensity traces of Fluo-4 over time at varying laser duty cycles, showing higher response amplitude at higher irradiance. Numbers in (a) depict the irradiance in W cm ^-2 . Stimuli were delivered as a 250 ms pulse to a 5 µm diameter circular area. (b) Dose-response curve showing higher calcium response amplitudes at higher light intensities. Values shown represent the peak response amplitude. Error bars represent the standard error of the mean of at least six individual cells. FIGS.8A - 8D – MM-induced ICW do not cause apoptosis or necrosis. Cells were treated with MM 1 (8 µM) as described in Methods and stained with Fluo-4 to track calcium flux, propidium iodide (PI) to track membrane poration and cell death, and cellMask plasma membrane stain to distinguish and track individual cells. (a) Positive control for apoptotic cell death with characteristic cell shrinkage (pyknosis) incurred by consecutive cell exposure to blue light (488 nm, irradiance of ~60 W cm ^-2 rastered across the entire image for a period of 30 min). (b) Positive control for necrotic cell death incurred by treatment of cells with MM 1 and irradiation with UV light (365-385 nm, ~0.16 W cm ^-2 for 5 min). Cell death is indicated by rapid PI uptake. (c) Negative control showing morphology of undisturbed, healthy cells. (d) A small colony of cells shown just before and 30 min after a typical stimulation experiment with the site of stimulation marked (circle, second image on top row). All scale bars are 50 µm and apply to the images in their sub-figure. FIGS.9A & 9B – MM-induced ICW do not have toxic effects on stimulated cell populations. Ibidi microscope dishes were photolithographically patterned with polydimethylsiloxane to prevent cell attachment except for in a gridded array pattern, resulting in isolated HEK293-colonies of defined size and geometry ³⁸ . These colonies were imaged 3 days after being seeded following i) no treatment (negative control; NC), ii) stimulation with MM 1 and light on day 2 (10 single-cell stimulations per colony, 3.2×10 ² W cm ^-2 ; Treated) , or iii) irradiation with UV light (365-385 nm, ~0.16 W cm ^-2 ) for 5 min on day 3 (positive control; PC). (a) Bright field (left) and fluorescent (right) images of representative colonies from each treatment showing the onset of PI uptake into colonies in the PC group and no substantial uptake post stimulation in the treated cells. Scale bar is 200 µm and applies to all images. (b) Calculated PI fluorescent intensity. Error bars indicate standard deviation. n=3 colonies for each group. FIGS. 10A & 10B – Toxicity at high exposure times and high laser power. (a) Confocal microscope images of HEK293 cells treated with MM 1 and Fluo-4 calcium tracking dye after a 4 s light pulse of 400 nm light at 6.4×10 ² W cm ^-2 . Thirty minutes after treatment, the calcium signal has not returned to homeostasis, and membrane blebbing is apparent (red arrows). (b) Confocal images of HEK293 cells treated with MM 1 and Fluo-4 calcium tracking dye after laser pulses of 3.2×10 ² W cm- ² for 1 s. After 30 min, the calcium signal has returned to homeostatic levels, and the stimulated cell and surrounding cells display no apparent damage. Scale bars are 50 µm and apply to all images in their sub-figure. The white dotted circles indicate the area of stimulation. FIGS. 11A & 11B – ICW in N2A cells after stimulation with MM 1 and light. (a) Confocal images of N2A cells treated with MM 1 (blue) and calcium tracking dye (Fluo-4; green). The white circle in the top-left image depicts the area to which stimulus was delivered. The scale bar is 50 µm and applies to all images. (b) Fluo-4 fluorescence traces of N2A cells treated with MM 1 and stimulated with 250 ms pulse of 400 nm light delivered to a 5 µm diameter circular region of interest at 3.2×10 ² W cm ^-2 stimulation power. FIGS. 12A & 12B – ICW in HeLa cells after stimulation with MM 1 and light. (a) Confocal images of HeLa cells treated with MM 1 (blue) and Fluo-4 calcium tracking dye (green). The white circle in the bottom-left image depicts the area to which light stimulus was delivered. Scale bar is 50 µm and applies to all images. (b) Fluo-4 fluorescence traces of HeLa cells treated with MM 1 and stimulated with 250 ms pulse of 400 nm light delivered to a 5 µm diameter circular region of interest at 3.2×10 ² W cm ^-2 stimulation power. FIG.13 – Sample UV-Vis spectra of each MM taken at 16 µM in spectral-grade water. FIGS. 14A-14J – Mechanistic study of MM-induced ICW. (a) Schematic of possible mechanisms by which calcium can enter the cytoplasm. Prepared with Biorender.com. (b) Confocal microscope images of HEK293 cells treated with MM 1, MitoTracker Green, ER Tracker Red, and CellMask Deep Red. Scale bars are both 20 µm and apply to the images in the same row. (c-h) Calcium waves elicited by MM 1-treated cells (c) in calcium-free PBS, (d) in RR (1 µM), (e) in Gd ³⁺ (50 µM), (f) after treatment of cells with Th (1 µM), (g) in Ry (100 µM), (h) in XeC (25 µM), (i) in U-73 (10 µM), (j) after pre-treatment of cells with Cyto D (2 µM). The solid line represents the calcium profiles averaged from six independent cells. The shaded region represents the standard error of the mean (n=6). Stimuli were presented after 30 s of imaging in each case, and the time of stimulus presentation is indicated by the vertical cyan line. For all plots, the black trace shows a positive control consisting of MM 1-treated cells in typical imaging buffer recorded on the same day. All stimuli were delivered with a pulse width of 250 ms to a circular area of diameter 5 µm at a power ranging from 3.2×10 ² W cm ^-2 to 5.1×10 ² W cm ^-2 . For all plots, the cyan line indicates the time of stimulus presentation. Controls and experimental groups were imaged and stimulated on the same day using the same conditions and with the same batch of cells. Error bars in the bar graphs represent the standard deviation of the mean of n=3 experiments (at least 6 stimulated cells per experiment). Statistical analyses were performed using a one-tailed Welch’s t-test. * P-value < 0.05, ** P-value < 0.01, *** P-value < 0.001, **** P-value < 0.0001. FIGS. 15A-15F – Intracellular location of each MM. (a) Confocal images of HEK293 cells incubated with each MM, and different organelle-targeting dyes, namely ER-Tracker Red (ER), MitoTracker Green (mitochondria), and cellMask (plasma membrane), showing that MM preferentially distribute to the ER. The 50 µm scale bar applies to all images in the first four rows. (b) Pixel overlap maps of MM 1 fluorescence paired with fluorescence from organelle-targeted dyes. Blue color indicates pixels with fluorescence from MM 1 but not dye. Red color indicates pixels with fluorescence from dye but not MM 1. Gray color indicates pixels with overlapping fluorescence from both MM 1 and dye. Left: cell membrane; middle: ER; right: mitochondria. Scale bar is 20 µm and applies to all images. Percent volumetric coverage of each organelle by (c) MM 1, (d) MM 2, (e) MM 3, and (f) MM 4. MM/ER depicts the percentage of MM found in the ER, while ER/MM depicts the percentage of ER covered with MM. MM/CM and MM/Mito depict the proportion of MM found in the cell membrane and mitochondria, respectively. FIG. 16 – Microscopy images revealing the intracellular localization of MM 1 (blue), MitoTracker Green (green), ER-Tracker-Red (red), and cellMask plasma membrane dye (cyan) in HeLa cells. Scale bar is 50 µm and applies to all images. FIGS. 17A-17F - MM-induced calcium waves cause localized calcium release, contraction, and beating in cardiomyocytes. (a) Confocal microscope images of a single myocyte treated with MM 1 and ER Tracker Red. The scale bar is 10 µm and applies to all images. (b) Confocal microscope images showing Fluo-4 fluorescence, revealing calcium activity in cardiomyocytes before and after stimulation. The scale bar is 50 µm and applies to all images. The white circle represents the stimulation region. (c) Kymographs representative of cardiac myocyte contractile responses from the same cells shown in (b). The line profiles from which kymographs 1 and 2 were taken are shown as double-sided arrows in the bright field image. Kymographs 1 and 2 were taken from the stimulated cell and an adjacent cell, respectively. The scale bar in the bright field image is 50 µm. Kymograph 1 shows local contraction in the stimulated cell (top arrow in 1), indicated by a convergence of the edges in the kymograph plot. Both kymographs 1 and 2 show periodic beating in the stimulated cell and surrounding cell (bottom arrow in 1 and arrow in 2). (d-f) Normalized fluorescence intensity change of Fluo-4 in cardiomyocytes adjacent to stimulated cardiomyocytes that were treated with (d) MM 1 alone, (e) MM 1 and U-73 (10 µM), and (f) MM 1 in calcium-free PBS. For each condition, n=50 cells were used. The x-axis label in (f) also applies to (d-e). All stimulation experiments were performed with a stimulation time of 250 ms at 5.1×10 ² W cm ^-2 in a circular region of 5 µm diameter using a 400 nm laser. In all plots, the cyan line indicates the time of stimulus presentation. FIGS. 18A-18I – Heatmap plots (a-c), temporal spike frequencies (d-f), and individually plotted traces (g-i) of cardiomyocytes adjacent to a cell stimulated with (a,d,g) MM 1 + light, (b,e,h) MM 1 + light in 10 µM U-73, and (c,f,i) MM 1 + light in PBS. Light stimulation was performed using a 5.1×10 ² W cm ^-2 250 ms pulse of 400 nm laser light delivered to a 5 µm diameter area. The histograms in (d-f) indicate the time distributions of calcium spikes in cardiomyocytes identified by a peak detection algorithm (see Methods). Different colors in the individual traces in (g-f) indicate individual cells. FIGS. 19A & 19B – Different phenotypes of cardiac myocyte activation in surrounding cells. Response phenotypes of individual colonies of cardiac myocytes showing (a) enhanced firing due to membrane depolarization and (b) synchronous calcium increase. Black traces indicate the stimulated cell. Red traces indicate adjacent cells in a colony. Light stimulation was performed using a 5.1×10 ² W cm ^-2 250 ms pulse of 400 nm laser light delivered to a 5 µm diameter area. FIGS. 20A-20N - MM induce ICW and muscle contraction in vivo. (a) Image of a Hydra loaded into a microfluidic chamber with anatomical regions marked. Scale bar is 100 µm and applies to (a-c). (b) MM 1 (24 µM) loaded into Hydra for 24 h. (c) A Hydra expressing GCaMP7b in endodermal epitheliomuscular cells. The stimulation regions used for Protocols I and II are marked. Protocol I was used for body column stimulation (1 s pulse to a 10 µm diameter circular area) to trigger regional ICW. Protocol II was used for oral region stimulation (2 s pulse to the oral region, ~1000-2000 µm ² ) to trigger whole-body contraction. (d) A regional ICW in a Hydra treated with MM 1 and stimulated with 405-nm light via Protocol I. The indicated times represent the time after stimulation at which the image was taken. Scale bar applies to both images and is 100 µm. (e-i) Responses observed from Hydra treated with (e) MM 1, (f) MM 2, (g) MM 3, (h) MM 4, or (i) '062^FRQWURO^^³&´^^DQG^ stimulated for 1 s using Protocol I. Bold, colored traces represent the average trace (n=25 across 5 Hydra). Gray traces represent individual experiments. (j) Bar graph showing ICW response rate and (k) box-and-whisker plot showing ICW delay time of Hydra stimulated using Protocol I across MM treatment conditions (n=25 experiments across at least 5 Hydra per condition). ICW responses were defined as ^F/^ _^ > 1. (l) Representative contraction in a Hydra treated with MM 2 and stimulated via Protocol II. Scale bar applies to both images and is 100 µm. (m) Representative GCaMP7b fluorescence trace in a Hydra treated with MM 2 and stimulated using Protocol II. (n) Bar graph showing contractile response rates across treatment conditions for Hydra stimulated for 2 s using Protocol II (at least 50 experiments across >5 Hydra per condition). Error bars in bar graphs represent the standard error of the mean. See Example 6 for more info on the calculation of ICW and contractile response rates. For all plots, cyan lines indicate the time of stimulus with 405-nm light (9.0×10 ² W cm ^-2 ), during which no data was collected. * P-value < 0.05, ** P-value < 0.01, *** P-value < 0.001, **** P-value < 0.0001. FIG. 21 - Representative results for regional ICW elicited in MM-treated Hydra vulgaris. Representative images (left) and normalized fluorescence intensity traces of GCaMP7b (right) of Hydra treated with each MM (24 µM) or DMSO (0.3% v/v). Scale bar is 100 µm and applies to all images. Traces were taken from the area of stimulation shown by the white dotted circles. Hydra were stimulated at 9.0×10 ² W cm ^-2 power with a 405 nm laser in a 10 µm diameter circular area for 1 s (Protocol I). FIG. 22A-22F - Peak analysis of MM 1-treated Hydra (rotation rate of 3 MHz). (a) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 1 + light (Protocol II). , The contractions (peaks) most often occur in concert with stimuli (cyan lines). (b) Temporal location of contraction onset relative to presentation of light stimulus. (c) Temporal location of contraction burst peaks relative to presentation of light stimulus. (d) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 1 and sham light stimulus (same protocol with 0% laser duty cycle). Contractions do not occur in concert with sham stimulus. (e) Temporal location of contraction onset peaks relative to presentation of sham light stimulus. (f) Temporal location of contraction burst peaks relative to presentation of sham light stimulus. Histograms were calculated across all collected data (at least 50 stimulation or sham stimulation attempts in at least 5 Hydra). FIG.23A-23F - Peak analysis of MM 2-treated Hydra (fastest MM; rotation rate of 43 MHz). (a) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 2 + light (Protocol II). The contractions (peaks) occur in concert with stimuli (cyan lines). (b) Temporal location of contraction onset relative to presentation of light stimulus. (c) Temporal location of contraction burst peaks relative to presentation of light stimulus. (d) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 2 and sham light stimulus (same protocol with 0% laser duty cycle). Contractions do not occur in concert with sham stimulus. (e) Temporal location of contraction onset peaks relative to presentation of sham light stimulus. (f) Temporal location of contraction burst peaks relative to presentation of sham light stimulus. Histograms were calculated across all collected data (at least 50 stimulation or sham stimulation attempts in at least 5 Hydra). FIG.24A-24F - Peak analysis of MM 3-treated Hydra (slow MM; rotation rate of 10 ^-1 Hz). (a) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 3 + light (Protocol II). The contractions (peaks) occasionally follow stimuli (cyan lines). (b) Temporal location of contraction onset relative to presentation of light stimulus. (c) Temporal location of contraction burst peaks relative to presentation of light stimulus. (d) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 3 and sham light stimulus (same protocol with 0% laser duty cycle). Contractions do not occur in concert with sham stimulus. (e) Temporal location of contraction onset peaks relative to presentation of sham light stimulus. (f) Temporal location of contraction burst peaks relative to presentation of sham light stimulus. Histograms were calculated across all collected data (at least 50 stimulation or sham stimulation attempts in at least 5 Hydra). FIG. 25A-25F - Peak analysis of MM 4-treated Hydra (non-unidirectional MM; rotation rate of 3 MHz). (a) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 4 + light (Protocol II). The contractions (peaks) most often occur in concert with stimuli (cyan lines). (b) Temporal location of contraction onset relative to presentation of light stimulus. (c) Temporal location of contraction burst peaks relative to presentation of light stimulus. (d) Characteristic GCaMP7b fluorescence trace of Hydra treated with MM 4 and sham light stimulus (same protocol with 0% laser duty cycle). (e) Temporal location of contraction onset peaks relative to presentation of sham light stimulus. Contractions do not occur in concert with sham stimulus. (f) Temporal location of contraction burst peaks relative to presentation of sham light stimulus. Histograms were calculated across all collected data (at least 50 stimulation or sham stimulation attempts in at least 5 Hydra). FIG. 26A-26F - Peak analysis of DMSO-treated control Hydra. (a) Characteristic GCaMP7b fluorescence trace of Hydra treated with DMSO (0.3% v/v) + light (Protocol II). The contractions (peaks) occasionally follow stimuli (cyan lines) due to the photosensitivity of the oral region. (b) Temporal location of contraction onset relative to presentation of light stimulus. (c) Temporal location of contraction burst peaks relative to presentation of light stimulus. (d) Characteristic GCaMP7b fluorescence trace of Hydra treated with DMSO and sham light stimulus (same protocol with 0% laser duty cycle). Contractions do not occur in concert with sham stimulus. (e) Temporal location of contraction onset peaks relative to presentation of sham light stimulus. (f) Temporal location of contraction burst peaks relative to presentation of sham light stimulus. Histograms were calculated across all collected data (at least 50 stimulation or sham stimulation attempts in at least 5 Hydra). FIG. 27 - Normalized fluorescent intensity trace of a HEK293 cell treated with MM 1 as described in the Methods section and excited by a Coherent Chameleon Discovery femtosecond laser operating at ~1.5×102 W cm ^-2 at 405 nm and imaged at 20 fps. The cyan line indicates the time of stimulation. The sharp vertical line likely reflects a fluorescence resonant energy transfer effect between the MM and calcium imaging dye (Fluo-4) during laser excitation, not visible in other experiments because images were not collected during stimulation. FIG.28 - Normalized fluorescence intensity traces of C2C12 myoblasts treated with MM 1 (8 ^0^^DQG^)OXR-^^^^^^0^^DQG^VWLPXODWHG^ZLWK^^^^^QP^OLJKW^DW^^^ ^^î^^^^^:^FP ^í2 . FIG.29 - Localization of MM 1 with Fluo-4 and CellMask. FIG. 30 - Normalized fluorescence intensity traces of C2C12 myoblasts treated with MM 1 (8 ^0^^DQG^)OXR-^^^^^^0^^DQG^VWLPXODWHG^ZLWK^^^^^QP^OLJKW^DW^^^ ^î^^^^^:^FP ^í2 (For Lp 70 traces) or 4.6 × 102 W cm ^í2 (For Lp 100 traces) with different duration. FIG. 31 - ROS generation for all MMs and DMSO compared to 1 min ^{stimulation with UV} light and treatment with 1 mM H2O2 for 1 hour. F ^{IG. 32 -} Calcium release of MM 3 at 3x concentration. FIG. 33 - Calcium release in C2C12 cells before and after treatment with a combination of 100 µM gallein and 1 µM FR900359. FIGS.34A & 34B - Fluo-4 expression in myotubes incubated in differentiation media (a), and normal growth media (b). FIG.35 - Flow chart for the image subtraction process. First, the background is subtracted from the traces to account for drift during the course of the experiment (top row). After this, the traces are zeroed at the point of stimulation, and the area is calculated from the point of stimulation until the end of the experiment to yield the contraction magnitude. (bottom row). FIGS. 36A-36D - MMs cause intracellular calcium waves in C2C12 myoblasts. a) MM 1 (unidirectional, ~3 MHz) structure showing rotor and stator. b) Rotation cycle of a MM. c) Confocal microscope images of C2C12 myoblasts with MM and labeled with Fluo-4. Stimulated areas are indicated by the red arrows immediately before stimulation and 10 s after stimulation. Scale bar = 30 µm. d) Average normalized fluorescence intensity trace of stimulated C2C12 cells myoblasts treated with either DMSO (n=6) or MM 1 (n=7) and stimulated with 400-nm laser light for 500 ms. Laser stimulation is shown by the cyan line. FIGS. 37A-37C - Calcium release in C2C12 myoblasts varies with MM type. a) Structure of MM 2 (bidirectional, ~3 MHz) and MM 3 (unidirectional, ~0.1 Hz) control motors, b) their UV-Vis spectrum compared to MM 1, and c) their elicited calcium release when stimulated with 400-nm light for 500 ms. d) Calcium release vs ROS generation elicited by MM 1 when cells were treated with various concentrations of ROS scavengers thiourea (TU) and sodium azide (SA). 1x concentration of scavengers is 50 mM TU and 1.25 mM SA. FIGS. 38A-38F - Calcium release in C2C12 myoblasts occurs by means of the IP3 pathway. Average normalized fluorescence intensity traces of C2C12 myoblasts before and after treatment with a) 10 µM U-^^^^^^^3/&^LQKLELWRU^^^E^^^^^^^0^JDOOHLQ^^*3&5ȕȖ ^LQKLELWRU^^^F^^^^^0^)5^^^^^^^^*3&5Į^ inhibitor), d) 200 µM cAMPS-Rp (cAMP antagonist, inhibits PKA activation), e) 100 µM SQ22536 (adenylyl cyclase inhibitor), and f) 1 µM nintedanib (RTK inhibitor). FIGS.39A & 39B - Calcium responses decrease over nine days in developing C2C12 cells. a) Brightfield and confocal microscopy images of C2C12 cells labeled with Fluo-4 after various days of growth. Stimulated areas are indicated by the red arrows immediately before stimulation and 5 s after stimulation. b) Average normalized fluorescence intensity trace of cells after each day of growth (n = 9). Scale bar is 300 µm for brightfield images and 30 µm for fluorescence images. FIGS. 40A-40D - MMs induce contraction in C2C12 myotubes. a) Confocal microscopy images of Fluo- 4 and b) image subtraction of brightfield images to highlight calcium release and contractile motion in three stimulated myotubes (indicated by the red arrows) immediately before stimulation (t = 0) for 1.5 s with 400-nm light, as well as 10 s and 120 s after stimulation. Scale bar = 30 µm. c) Magnitude of contraction of MM 1 compared to DMSO, MM 2, MM 3, and cells treated with 10 µM U-73122. d) Mechanism of skeletal muscle cell contraction. FIGS.41A & 41B - Cy7.5-amine and Cy7-amine structure and spectra. A) Chemical structure and expected molecular plasmon modes TMP and LMP. B) Absorption spectra of cyanine molecules and assignment of vibrational collective oscillation (vibronic mode), LMP and TMP. The LED light at 730 nm excited mostly the vibrational mode in Cy7.5-amine but not in Cy7-amine. DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS Provided herein are methods and methods of treatment that have been demonstrated to generate ICWs. These methods and methods of treatment may be useful to regulate calcium signaling pathways. These methods may be used to treat one or more diseases or disorders for which generating ICWs and/or regulating calcium signaling pathways may be useful. In some embodiments, these diseases or disorders include neurological and neurodegenerative diseases. Furthermore, these methods may represent an improvement over those known in the art as the therapeutic methods may be more efficacious than, be longer acting than, be more potent than, produce fewer side effects than, and/or have other useful pharmacological, physical, or chemical properties. These and more details will be discussed in more detail below. I. Intercellular Calcium Waves (ICWs) and Methods of Regulating Calcium Signaling Intercellular calcium waves (ICWs) are triggered by a variety of stimuli and involve the release of Ca ²⁺ from internal stores (Leybaert & Sanderson). In some embodiments, the present disclosure provides methods of using a light-stimulated MM to generate an ICW. In some embodiments, the methods use vibronic-driven action. In some embodiments, the MM comprise a Feringa-type or a hemithioindigo-type MM. 9LEURQLF^ FRXSOLQJ^^ DOVR^ WHUPHG^ ³YLEURQLF^PRGH´^^ UHIHUV^ WR^ DQ^ DOLJQPHQW^ RI^ YLEUDWLRQDO^ DQG^ electronic modes, which may also be known as plasmonic modes and phonon modes, respectively. In a PROHFXOH^^WKH^YLEURQLF^PRGH^PD\^DOVR^EH^GHVFULEHG^DV^D^³PRO HFXODU^SODVPRQ´^FRXSOHG^WR^D^³PROHFXODU^ SKRQRQ´^^8SRQ^DEVRUEDQFH^RI^HQHUJ\^^YLEUDWLRQDO^PRGHV^RI^WK H^DWRPV^RI^D^PROHFXOH^PD\^K\EULGL]H^with the electronic transitions of the molecule to induce a vibronic mode. ³+HPLWKLRLQGLJR´^ UHIHUV^ WR^ D^ photoswitch in which the central photoisomerizable C=C double bond connects an indigo or thioindigo half with a stilbene moiety. ³)HULQJD-W\SH´^UHIHUV^Wo sterically overcrowded alkenes used as a chiroptical trigger molecules. Upon irradiation at the appropriate wavelength, the molecules undergo cis-trans photoisomerizations that simultaneously result in helix reversal. In some embodiments, the compound may be an organic molecule. In particular, the organic compound may exhibit either or both of a longitudinal or a transverse molecular plasmon. In certain embodiments, the moiety that generates a vibronic-driven action has a net dipole, has a high degree of symmetry across the longitudinal and/or transverse axis, and has a resonance structure through a pi- bonded system. The net dipole of the moiety, in some embodiments, may be due to a charge, such as a cation, anion, radical cation, or radical anion. In some embodiments, the net dipole is due to a radical. In some embodiments, the moiety that generates a vibronic-driven action may be an organic dye. In particular, the moiety that generates a vibronic-driven action may be a cyanine dye. In other embodiments, the moiety that generates a vibronic-driven action may be a thiazine dye such as methylene blue, a boron containing dye such as BODIPY, a xanthene dye such as fluorescein or rose bengal, a triarylmethylene such as phenol red, or a dye such as nile red. Cyanine dyes have been used in photothermal and photodynamic therapies and they are readily accepted in biological and medicinal studies. (Mishra et al., 2000; Li et al., 2021; Shi et al., 2016; Lange et al., 2021; Bilici et al., 2021). FIG. 41A shows the chemical structure and absorption spectra of two aminocyanines, Cy7-amine and Cy7.5-amine. Without being bound by theory, the amine moieties, which are protonated at physiological pH, may promote association with the lipid bilayer charged surfaces. Cyanine structures are characterized by an odd-numbered polyene linker connecting two nitrogen-containing heterocycles with unusual photophysical properties. The absorption spectrum of cyanines is dominated by an absorption band in the visible/NIR electromagnetic spectrum with a shoulder located at higher energy (shorter wavelength). The Cy7.5-amine, in contrast to Cy7-amine, has an additional benzene ring that increases the conjugation, causing a red-shifting of the absorption by ~40 nm relative to Cy7-amine. The origin of the sub-bands in cyanines have been thoroughly studied, which without being bound by theory it may be concluded that the presence of the shoulder next to the large absorption band LV^³SULPDULO\^GHWHUPLQHG^E\^D^GRPLQDQW^YLEUDWLRQ^DVVRFLDWHG ^ZLWK^LWs polymethine chain rather than a FROOHFWLRQ^RI^VLQJO\^H[FLWHG^YLEUDWLRQV´^^0XVWURSK^DQG^7RZQ V^^^^^^^^^7KH^YLEURQLF^EHKDYLRU^^WKURXJK^ the coupling of electronic and vibrational states, is a feature of the conjugated-backbone-near- symmetrical cyanines such as in Cy7-amine and C7.5-amine. In the case of conjugated-backbone- unsymmetrical cyanines, the absorption curves do not exhibit a vibrational fine structure, analogous to most spectra of merocyanines (Mustroph, 2021). Without being bound by theory, the vibronic mode in symmetrical cyanine structures is thought to result from the coupling of a dominant collective oscillation of electronic excitation (molecular plasmon) to a dominant collective vibrational excitation (phonon). The shoulders at ~ 730 nm and ~ 690 nm in the absorption spectrum of Cy7.5-amine and Cy7-amine, respectively, correspond to this collective vibrational mode. In some embodiments, the energy source used to induce the ICW is electromagnetic radiation, such as gamma rays, X-rays, ultraviolet (UV) light, visible (Vis) light, near-infrared (NIR) light, infrared light (IR), microwaves, or radio waves. In some embodiments, the energy source used to induce the ICW may be light with a wavelength from about 250 nm to about 2,000 nm. In some embodiments, the wavelength is from about 350 nm to about 1,000 nm or about 450 nm to about 900 nm. In some embodiments, the wavelength of the light may be about 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100, 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, or 2000 nm, or any range derivable therein. In some embodiments, the wavelength of light is about 400 nm. In some embodiments, other types of stimuli including electric fields, ionizing radiation, magnetic fields, mechanical forces, or ultrasound may also be used to induce an ICW. The present methods contemplate using different intensities or duration of light. The intensity of the light may be proportional to the effectiveness of the ICW at a particular wavelength. These intensities can range from 10 nW/cm ² to 1000 W/cm ² , from 100 nW/cm ² to 8 W/cm ² , or from about 10 µW/cm ² to about 5 W/cm ² . The intensity can be from about 10 nW/cm ² , 50 nW/cm ² , 100 nW/cm ² , 250 nW/cm ² , 500 nW/cm ² , 750 nW/cm ² , 1 µW/cm ² , 10 µW/cm ² , 25 µW/cm ² , 50 µW/cm ² , 100 µW/cm ² , 200 µW/cm ² , 300 µW/cm ² , 400 µW/cm ² , 500 µW/cm ² , 600 µW/cm ² , 700 µW/cm ² , 800 µW/cm ² , 900 µW/cm ² , 1 W/cm ² , 10 W/cm ² , 100 W/cm ² , 200 W/cm ² , 400 W/cm ² , 500 W/cm ² , 600 W/cm ² , 800 W/cm ² , to about 1000 W/cm ² , or any range derivable therein. II. Indications A. Neurological Disorders In one embodiment, the calcium regulating MM may be used to treat a neurodegenerative or QHXURORJLFDO^GLVHDVH^RU^GLVRUGHU^^7KH^WHUP^³QHXURGHJHQHUDWL YH^GLVHDVH^RU^GLVRUGHU´^DQG^³QHXURORJLFDO^ GLVRUGHUV´^ HQFRPSDVV^ D^ GLVHDVH^ RU^ GLVRUGHU^ LQ^ ZKLFK^ WKH^ SHULSKHUDO^ QHUYRXV^ V\VWHP^ RU^ WKH^ FHQWUDO^ nervous system is principally involved. The methods provided herein may be used in the treatment of neurological or neurodegenerative diseases and disorders. As used herein, the terms ³QHXURGHJHQHUDWLYH^GLVHDVH^´^³QHXURGHJHQHUDWLYH^GLVRUGHU^ ´^³QHXURORJLFDO^GLVHDVH^´^DQG^³QHXURORJLFDO^ GLVRUGHU´^DUH used interchangeably. Examples of neurological disorders or diseases include, but are not limited to chronic neurological diseases such as diabetic peripheral neuropathy (including third nerve palsy, mononeuropathy, mononeuropathy multiplex, diabetic amyotrophy, autonomic neuropathy and thoracoabdominal neuropathy), Alzheimer's disease, age-related memory loss, senility, age-related dementia, Pick's disease, diffuse Lewy body disease, progressive supranuclear palsy (Steel-Richardson syndrome), multisystem degeneration (Shy-Drager syndrome), motor neuron diseases including amyotrophic lateral sclerosiV^ ^³$/6´^^^ GHJHQHUDWLYH^ DWD[LDV^^ FRUWLFDO^ EDVDO^ GHJHQHUDWLRQ^^ $/6- Parkinson's-Dementia complex of Guam, subacute sclerosing panencephalitis, Huntington's disease, 3DUNLQVRQ^^ V^ GLVHDVH^^ PXOWLSOH^ VFOHURVLV^ ^³^ 06´^ ^^^ V\QXFOHLQRSDWKLHV^^ SULPDU\^ SURJUHVVLYH^ DSKasia, striatonigral degeneration, Machado-Joseph disease/spinocerebellar ataxia type 3 and olivopontocerebellar degenerations, Gilles De La Tourette's disease, bulbar and pseudobulbar palsy, spinal and spinobulbar muscular atrophy (Kennedy's disease), primary lateral sclerosis, familial spastic paraplegia, Wernicke-Korsakoff's related dementia (alcohol induced dementia), Werdnig-Hoffmann disease, Kugelberg-Welander disease, Tay-Sach's disease, Sandhoff disease, familial spastic disease, Wohifart-Kugelberg-Welander disease, spastic paraparesis, progressive multifocal leukoencephalopathy, and prion diseases (including Creutzfeldt-Jakob, Gerstmann-Straussler- Scheinker disease, Kuru and fatal familial insomnia). Other conditions also included within the methods of the present disclosure include age-related dementia and other dementias, and conditions with memory loss including vascular dementia, diffuse white matter disease (Binswanger's disease), dementia of endocrine or metabolic origin, dementia of head trauma and diffuse brain damage, dementia pugilistica, and frontal lobe dementia. Also, other neurodegenerative disorders resulting from cerebral ischemia or infarction including embolic occlusion and thrombotic occlusion as well as intracranial hemorrhage of any type (including, but not limited to, epidural, subdural, subarachnoid, and intracerebral), and intracranial and intravertebral lesions (including, but not limited to, contusion, penetration, shear, compression, and laceration). Thus, the term also encompasses acute neurodegenerative disorders such as those involving stroke, traumatic brain injury, schizophrenia, peripheral nerve damage, hypoglycemia, spinal cord injury, epilepsy, and anoxia and hypoxia. B. Cancer and Hyperprolfierative Diseases While hyperproliferative diseases can be associated with any disease which causes a cell to begin to reproduce uncontrollably, the prototypical example is cancer. One of the key elements of cancer is that the cell’s normal apoptotic cycle is interrupted and thus agents that interrupt the growth of the cells are important as therapeutic agents for treating these diseases. In some embodiments, the cell membrane that may be disrupted is a human cell, such as a cancer cell. In some embodiments, the compounds of the disclosure may disrupt a human cell, such as an adipose cell. The methods described in the present disclosure contemplate the disruption of either or both a healthy cell or a cancerous cell. In this disclosure, the compounds described herein may be used to lead to decreased cell counts and as such can potentially be used to treat a variety of types of cancer lines. In some embodiments, the compounds described herein are contemplated to open the cell membrane. In further embodiments, the compounds described herein thus allow at least a second therapeutic agent to enter the cell. In some aspects, it is anticipated that the compounds described herein may be used to treat virtually any malignancy. Cancer cells that may be treated with the compounds of the present disclosure include but are not limited to cells from the skin, bladder, blood, bone, bone marrow, brain, breast, colon, esophagus, gastrointestine, gum, head, kidney, liver, lung, nasopharynx, neck, ovary, prostate, skin, stomach, pancreas, testis, tongue, cervix, or uterus. In addition, the cancer may specifically be of the following histological type, though it is not limited to these: neoplasm, malignant; carcinoma; carcinoma, undifferentiated; giant and spindle cell carcinoma; small cell carcinoma; papillary carcinoma; squamous cell carcinoma; lymphoepithelial carcinoma; basal cell carcinoma; pilomatrix carcinoma; transitional cell carcinoma; papillary transitional cell carcinoma; adenocarcinoma; gastrinoma, malignant; cholangiocarcinoma; hepatocellular carcinoma; combined hepatocellular carcinoma and cholangiocarcinoma; trabecular adenocarcinoma; adenoid cystic carcinoma; adenocarcinoma in adenomatous polyp; adenocarcinoma, familial polyposis coli; solid carcinoma; carcinoid tumor, malignant; branchiolo-alveolar adenocarcinoma; papillary adenocarcinoma; chromophobe carcinoma; acidophil carcinoma; oxyphilic adenocarcinoma; basophil carcinoma; clear cell adenocarcinoma; granular cell carcinoma; follicular adenocarcinoma; papillary and follicular adenocarcinoma; nonencapsulating sclerosing carcinoma; adrenal cortical carcinoma; endometroid carcinoma; skin appendage carcinoma; apocrine adenocarcinoma; sebaceous adenocarcinoma; ceruminous adenocarcinoma; mucoepidermoid carcinoma; cystadenocarcinoma; papillary cystadenocarcinoma; papillary serous cystadenocarcinoma; mucinous cystadenocarcinoma; mucinous adenocarcinoma; signet ring cell carcinoma; infiltrating duct carcinoma; medullary carcinoma; lobular carcinoma; inflammatory carcinoma; Paget's disease, mammary; acinar cell carcinoma; adenosquamous carcinoma; adenocarcinoma w/squamous metaplasia; thymoma, malignant; ovarian stromal tumor, malignant; thecoma, malignant; granulosa cell tumor, malignant; androblastoma, malignant; sertoli cell carcinoma; Leydig cell tumor, malignant; lipid cell tumor, malignant; paraganglioma, malignant; extra-mammary paraganglioma, malignant; pheochromocytoma; glomangiosarcoma; malignant melanoma; amelanotic melanoma; superficial spreading melanoma; malignant melanoma in giant pigmented nevus; epithelioid cell melanoma; blue nevus, malignant; sarcoma; fibrosarcoma; fibrous histiocytoma, malignant; myxosarcoma; liposarcoma; leiomyosarcoma; rhabdomyosarcoma; embryonal rhabdomyosarcoma; alveolar rhabdomyosarcoma; stromal sarcoma; mixed tumor, malignant; Mullerian mixed tumor; nephroblastoma; hepatoblastoma; carcinosarcoma; mesenchymoma, malignant; Brenner tumor, malignant; phyllodes tumor, malignant; synovial sarcoma; mesothelioma, malignant; dysgerminoma; embryonal carcinoma; teratoma, malignant; struma ovarii, malignant; choriocarcinoma; mesonephroma, malignant; hemangiosarcoma; hemangioendothelioma, malignant; Kaposi's sarcoma; hemangiopericytoma, malignant; lymphangiosarcoma; osteosarcoma; juxtacortical osteosarcoma; chondrosarcoma; chondroblastoma, malignant; mesenchymal chondrosarcoma; giant cell tumor of bone; Ewing's sarcoma; odontogenic tumor, malignant; ameloblastic odontosarcoma; ameloblastoma, malignant; ameloblastic fibrosarcoma; pinealoma, malignant; chordoma; glioma, malignant; ependymoma; astrocytoma; protoplasmic astrocytoma; fibrillary astrocytoma; astroblastoma; glioblastoma; oligodendroglioma; oligodendroblastoma; primitive neuroectodermal; cerebellar sarcoma; ganglioneuroblastoma; neuroblastoma; retinoblastoma; olfactory neurogenic tumor; meningioma, malignant; neurofibrosarcoma; neurilemmoma, malignant; granular cell tumor, malignant; malignant lymphoma; Hodgkin's disease; paragranuloma; malignant lymphoma, small lymphocytic; malignant lymphoma, large cell, diffuse; malignant lymphoma, follicular; mycosis fungoides; other specified non-Hodgkin's lymphomas; malignant histiocytosis; multiple myeloma; mast cell sarcoma; immunoproliferative small intestinal disease; leukemia; lymphoid leukemia; plasma cell leukemia; erythroleukemia; lymphosarcoma cell leukemia; myeloid leukemia; basophilic leukemia; eosinophilic leukemia; monocytic leukemia; mast cell leukemia; megakaryoblastic leukemia; myeloid sarcoma; and hairy cell leukemia. In certain aspects, the tumor may comprise an osteosarcoma, angiosarcoma, rhabdosarcoma, leiomyosarcoma, Ewing sarcoma, glioblastoma, neuroblastoma, or leukemia. III. Compounds The compounds of the present disclosure are shown, for example, above, in the summary of the invention section, the Examples section, and in the claims below. They may be made using the synthetic methods outlined in the Examples section. These methods can be further modified and optimized using the principles and techniques of organic chemistry as applied by a person skilled in the art. Such principles and techniques are taught, for example, in Smith, March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, (2013), which is incorporated by reference herein. In addition, the synthetic methods may be further modified and optimized for preparative, pilot- or large-scale production, either batch or continuous, using the principles and techniques of process chemistry as applied by a person skilled in the art. Such principles and techniques are taught, for example, in Anderson, Practical Process Research & Development – A Guide for Organic Chemists (2012), which is incorporated by reference herein. All the compounds of the present disclosure may in some embodiments be used for the prevention and treatment of one or more diseases or disorders discussed herein or otherwise. In some embodiments, one or more of the compounds characterized or exemplified herein as an intermediate, a metabolite, and/or prodrug, may nevertheless also be useful for the prevention and treatment of one or more diseases or disorders. As such unless explicitly stated to the contrary, all the compounds of the SUHVHQW^GLVFOVRXUH^DUH^GHHPHG^³DFWLYH^FRPSRXQGV´^DQG^³WKH UDSHXWLF^FRPSRXQGV´^WKDW^DUH^FRQWHPSODWHG^ for use as active pharmaceutical ingredients (APIs). Actual suitability for human or veterinary use is typically determined using a combination of clinical trial protocols and regulatory procedures, such as those administered by the Food and Drug Administration (FDA). In the United States, the FDA is responsible for protecting the public health by assuring the safety, effectiveness, quality, and security of human and veterinary drugs, vaccines and other biological products, and medical devices. In some embodiments, the compounds of the present disclosure have the advantage that they may be more efficacious than, be less toxic than, be longer acting than, be more potent than, produce fewer side effects than, be more easily absorbed than, more metabolically stable than, more lipophilic than, more hydrophilic than, and/or have a better pharmacokinetic profile (e.g., higher oral bioavailability and/or lower clearance) than, and/or have other useful pharmacological, physical, or chemical properties over, compounds known in the art, whether for use in the indications stated herein or otherwise. The compounds of the present disclosure may contain one or more asymmetrically-substituted carbon or nitrogen atom and may be isolated in optically active or racemic form. Thus, all chiral, diastereomeric, racemic form, epimeric form, and all geometric isomeric forms of a chemical formula are intended, unless the specific stereochemistry or isomeric form is specifically indicated. Compounds may occur as racemates and racemic mixtures, single enantiomers, diastereomeric mixtures and individual diastereomers. In some embodiments, a single diastereomer is obtained. The chiral centers of the compounds of the present disclosure can have the S or the R configuration. In some embodiments, the present compounds may contain two or more atoms which have a defined stereochemical orientation. Chemical formulas used to represent the compounds of the present disclosure will typically only show one of possibly several different tautomers. For example, many types of ketone groups are known to exist in equilibrium with corresponding enol groups. Similarly, many types of imine groups exist in equilibrium with enamine groups. Regardless of which tautomer is depicted for a given compound, and regardless of which one is most prevalent, all tautomers of a given chemical formula are intended. In addition, atoms making up the compounds of the present disclosure are intended to include all isotopic forms of such atoms. Isotopes, as used herein, include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include ¹³ C and ¹⁴ C. In some embodiments, the compounds of the present disclosure function as prodrugs or can be derivatized to function as prodrugs. Since prodrugs are known to enhance numerous desirable qualities of pharmaceuticals (e.g., solubility, bioavailability, manufacturing, etc.), the compounds employed in some methods of the invention may, if desired, be delivered in prodrug form. Thus, the disclosure contemplates prodrugs of the compounds of the present disclosure as well as methods of delivering prodrugs. Prodrugs of the compounds employed in the disclosure may be prepared by modifying functional groups present in the compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent compound. Accordingly, prodrugs include, for example, compounds described herein in which a hydroxy, amino, or carboxy group is bonded to any group that, when the prodrug is administered to a patient, cleaves to form a hydroxy, amino, or carboxylic acid, respectively. In some embodiments, the compounds of the present disclosure exist in salt or non-salt form. With regard to the salt form(s), in some embodiments the particular anion or cation forming a part of any salt form of a compound provided herein is not critical, so long as the salt, as a whole, is pharmacologically acceptable. Additional examples of pharmaceutically acceptable salts and their methods of preparation and use are presented in Handbook of Pharmaceutical Salts: Properties, and Use (2002), which is incorporated herein by reference. It will be appreciated that many organic compounds can form complexes with solvents in which they are reacted or from which they are precipitated or crystallized. These complexes are known as ³VROYDWHV^´^^:KHUH^WKH^VROYHQW^LV^ZDWHU^^WKH^FRPSOH[^LV^NQ RZQ^DV^D^³K\GUDWH^´^^,W^ZLOO^DOVR^EH^DSSUHFLDWHG^ that many organic compounds can exist in more than one solid form, including crystalline and amorphous forms. It is contemplated that the present methods include all different polymorphos of the compounds used herein. All solid forms of the compounds provided herein, including any solvates thereof are within the scope of the present invention. IV. Pharmaceutical Formulations and Routes of Administration In another aspect, for administration to a patient in need of such treatment, pharmaceutical formulations (also referred to as a pharmaceutical preparations, pharmaceutical compositions, pharmaceutical products, medicinal products, medicines, medications, or medicaments) comprise a therapeutically effective amount of the calcium regulating MM of the present disclsoure formulated with one or more excipients and/or drug carriers appropriate to the indicated route of administration. In some embodiments, the calcium regulating MM disclosed herein are formulated in a manner amenable for the treatment of human and/or veterinary patients. In some embodiments, formulation comprises admixing or combining one or more of the calcium regulating MM disclosed herein with one or more of the following excipients: lactose, sucrose, starch powder, cellulose esters of alkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesium stearate, magnesium oxide, sodium and calcium salts of phosphoric and sulfuric acids, gelatin, acacia, sodium alginate, polyvinylpyrrolidone, and/or polyvinyl alcohol. In some embodiments, e.g., for oral administration, the pharmaceutical formulation may be tableted or encapsulated. In some embodiments, the calcium regulating MM may be dissolved or slurried in water, polyethylene glycol, propylene glycol, ethanol, corn oil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodium chloride, and/or various buffers. In some embodiments, the pharmaceutical formulations may be subjected to pharmaceutical operations, such as sterilization, and/or may contain drug carriers and/or excipients such as preservatives, stabilizers, wetting agents, emulsifiers, encapsulating agents such as lipids, dendrimers, polymers, proteins such as albumin, nucleic acids, and buffers. Pharmaceutical formulations may be administered by a variety of methods, e.g., orally or by injection (e.g. subcutaneous, intravenous, and intraperitoneal). Depending on the route of administration, the calcium regulating MM disclosed herein may be coated in a material to protect the compound from the action of acids and other natural conditions which may inactivate the compound. To administer the active compound by other than parenteral administration, it may be necessary to coat the calcium regulating MM with, or co-administer the calcium regulating MM with, a material to prevent its inactivation. In some embodiments, the active calcium regulating MM may be administered to a patient in an appropriate carrier, for example, liposomes, or a diluent. Pharmaceutically acceptable diluents include saline and aqueous buffer solutions. Liposomes include water-in-oil-in-water CGF emulsions as well as conventional liposomes. The calcium regulating MM disclosed herein may also be administered parenterally, intraperitoneally, intraspinally, or intracerebrally. Dispersions can be prepared in glycerol, liquid polyethylene glycols, and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations may contain a preservative to prevent the growth of microorganisms. Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (such as, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, sodium chloride, or polyalcohols such as mannitol and sorbitol, in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate or gelatin. The calcium regulating MM disclosed herein can be administered orally, for example, with an inert diluent or an assimilable edible carrier. The calcium regulating MM of the present disclosure and other ingredients may also be enclosed in a hard or soft-shell gelatin capsule, compressed into tablets, or incorporated directly into the patient’s diet. For oral therapeutic administration, the calcium regulating MM disclosed herein may be incorporated with excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like. The percentage of the therapeutic calcium regulating MM in the compositions and preparations may, of course, be varied. The amount of the therapeutic calcium regulating MM in such pharmaceutical formulations is such that a suitable dosage will be obtained. The therapeutic calcium regulating MM may also be administered topically to the skin, eye, ear, or mucosal membranes. Administration of the therapeutic calcium regulating MM topically may include formulations of the calcium regulating MM as a topical solution, lotion, cream, ointment, gel, foam, transdermal patch, or tincture. When the therapeutic calcium regulating MM is formulated for topical administration, the calcium regulating MM may be combined with one or more agents that increase the permeability of calcium regulating MM through the tissue to which it is administered. Topical administration may also include administration to the mucosa membranes such as the inside of the mouth. Such administration can be directly to a particular location within the mucosal membrane such as a tooth, a sore, or an ulcer. Alternatively, if local delivery to the lungs is desired the therapeutic calcium regulating MM may be administered by inhalation in a dry-powder or aerosol formulation. In some embodiments, it may be advantageous to formulate parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic calcium regulating MM calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. In some embodiments, the specification for the dosage unit forms of the disclosure are dictated by and directly dependent on (a) the unique characteristics of the calcium regulating MM and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding such a therapeutic calcium regulating MM for the treatment of a selected condition in a patient. In some embodiments, the active calcium regulating MM are administered at a therapeutically effective dosage sufficient to treat a condition associated with a condition in a patient. For example, the efficacy of a calcium regulating MM can be evaluated in an animal model system that may be predictive of efficacy in treating the disease in a human or another animal. In some embodiments, the effective dose range for the therapeutic calcium regulating MM can be extrapolated from effective doses determined in animal studies for a variety of different animals. In some embodiments, the human equivalent dose (HED) in mg/kg can be calculated in accordance with the following formula (see, e.g., Reagan-Shaw et al.,FASEB J., 22(3):659-661, 2008, which is incorporated herein by reference): HED (mg/kg) = Animal dose (mg/kg) × (Animal Km/Human Km) Use of the Km factors in conversion results in HED values based on body surface area (BSA) rather than only on body mass. Km values for humans and various animals are well known. For example, the Km for an average 60 kg human (with a BSA of 1.6 m ² ) is 37, whereas a 20 kg child (BSA 0.8 m ² ) would have a Km of 25. Km for some relevant animal models are also well known, including: mice Km of 3 (given a weight of 0.02 kg and BSA of 0.007); hamster Km of 5 (given a weight of 0.08 kg and BSA of 0.02); rat Km of 6 (given a weight of 0.15 kg and BSA of 0.025) and monkey Km of 12 (given a weight of 3 kg and BSA of 0.24). Precise amounts of the therapeutic composition depend on the judgment of the practitioner and are specific to each individual. Nonetheless, a calculated HED dose provides a general guide. Other factors affecting the dose include the physical and clinical state of the patient, the route of administration, the intended goal of treatment and the potency, stability and toxicity of the particular therapeutic formulation. The actual dosage amount of a calcium regulating MM of the present disclosure or composition comprising a calcium regulating MM of the present disclosure administered to a patient may be determined by physical and physiological factors such as type of animal treated, age, sex, body weight, severity of condition, the type of disease being treated, previous or concurrent therapeutic interventions, idiopathy of the patient and on the route of administration. These factors may be determined by a skilled artisan. The practitioner responsible for administration will typically determine the concentration of active ingredient(s) in a composition and appropriate dose(s) for the individual patient. The dosage may be adjusted by the individual physician in the event of any complication. In some embodiments, the therapeutically effective amount typically will vary from about 0.001 mg/kg to about 1000 mg/kg, from about 0.01 mg/kg to about 750 mg/kg, from about 100 mg/kg to about 500 mg/kg, from about 1 mg/kg to about 250 mg/kg, from about 10 mg/kg to about 150 mg/kg in one or more dose administrations daily, for one or several days (depending of course of the mode of administration and the factors discussed above). Other suitable dose ranges include 1 mg to 10,000 mg per day, 100 mg to 10,000 mg per day, 500 mg to 10,000 mg per day, and 500 mg to 1,000 mg per day. In some embodiments, the amount is less than 10,000 mg per day with a range of 750 mg to 9,000 mg per day. In some embodiments, the amount of the active calcium regulating MM the pharmaceutical formulation is from about 2 to about 75 weight percent. In some of these embodiments, the amount is from about 25 to about 60 weight percent. Single or multiple doses of the agents are contemplated. Desired time intervals for delivery of multiple doses can be determined by one of ordinary skill in the art employing no more than routine experimentation. As an example, patients may be administered two doses daily at approximately 12- hour intervals. In some embodiments, the agent is administered once a day. The agent(s) may be administered on a routine schedule. As used herein a routine schedule refers to a predetermined designated period of time. The routine schedule may encompass periods of time which are identical, or which differ in length, as long as the schedule is predetermined. For instance, the routine schedule may involve administration twice a day, every day, every two days, every three days, every four days, every five days, every six days, a weekly basis, a monthly basis or any set number of days or weeks there-between. Alternatively, the predetermined routine schedule may involve administration on a twice daily basis for the first week, followed by a daily basis for several months, etc. In other embodiments, the invention provides that the agent(s) may be taken orally and that the timing of which is or is not dependent upon food intake. Thus, for example, the agent can be taken every morning and/or every evening, regardless of when the patient has eaten or will eat. V. Methods of Treatment The compositions utilized in methods of the disclosure are preferably administered to a mammal (e.g., rodent, human, non-human primates, canine, bovine, ovine, equine, feline, etc.) in an effective amount, that is, an amount capable of producing a desirable result in a treated subject (e.g., slowing, stopping, reducing or eliminating one or more symptoms or underlying causes of disease). Toxicity and therapeutic efficacy of the compositions utilized in methods of the disclosure can be determined by standard pharmaceutical procedures. As is well known in the medical and veterinary arts, dosage for any one animal depends on many factors, including the subject's size, body surface area, body weight, age, the particular composition to be administered, time and route of administration, general health, the clinical symptoms and other drugs being administered concurrently. In some embodiments, amount of the calcium regulating MM used is calculated to be from about 0.01 mg to about 10,000 mg/day. In some embodiments, the amount is from about 1 mg to about 1,000 mg/day. In some embodiments, these dosings may be reduced or increased based upon the biological factors of a particular patient such as increased or decreased metabolic breakdown of the drug or decreased uptake by the digestive tract if administered orally. Addtionally, the calcium regulating MM may be more efficacious and thus a smaller dose is required to achieve a similar effect. Such a dose is typically administered once a day for a few weeks or until sufficient achieve clinical benefit. The therapeutic methods of the disclosure (which include treatment for neurological disorders) in general include administration of a therapeutically effective amount of the compositions utilized in methods of the disclosure to a subject in need thereof, including a mammal, particularly a human. Such treatment will be suitably administered to subjects, particularly humans, suffering from, having, susceptible to, or at risk for a disease, disorder, or symptom thereof. Determination of those subjects "at risk" can be made by any objective or subjective determination by a diagnostic test or opinion of a subject or health care provider (e.g., genetic test, enzyme or protein marker, family history, and the like). It is envisioned that the therapeutic methods described herein may be used in combination therapies with one or more additional therapies or a compound which mitigates one or more of the side effects experienced by the patient. It is common in the field of medicine to combine therapeutic modalities. The following is a general discussion of therapies that may be used in conjunction with the therapies of the present disclosure. To treat diseases or disorders using the methods and compositions utilized in methods of the disclosure, one would generally contact a cell or a subject with a calcium regulating MM and at least one other therapy. These therapies would be provided in a combined amount effective to achieve a reduction in one or more disease parameter. This process may involve contacting the cells/subjects with both agents/therapies at the same time, e.g., using a single composition or pharmacological formulation that includes both agents, or by contacting the cell/subject with two distinct compositions or formulations, at the same time, wherein one composition includes the MM and the other includes the other agent. Alternatively, the MM described herein may precede or follow the other treatment by intervals ranging from minutes to weeks. One would generally ensure that a significant period of time did not expire between the times of each delivery, such that the therapies would still be able to exert an advantageously combined effect on the cell/subject. In such instances, it is contemplated that one would contact the cell with both modalities within about 12–24 hours of each other, within about 6–12 hours of each other, or with a delay time of only about 1–2 hours. In some situations, it may be desirable to extend the time period for treatment significantly; however, where several days (2, 3, 4, 5, 6 or 7) to several weeks (1, 2, 3, 4, 5, 6, 7 or 8) lapse between the respective administrations. It also is conceivable that more than one administration of either the MM or the other therapy will be desired. Various combinations may be employed, where a compound of the present disclosure is ³A^´ and the other therapy is ³B,´ as exemplified below: A/B/A B/A/B B/B/A A/A/B B/A/A A/B/B B/B/B/A B/B/A/B A/A/B/B A/B/A/B A/B/B/A B/B/A/A B/A/B/A B/A/A/B B/B/B/A A/A/A/B B/A/A/A A/B/A/A A/A/B/A A/B/B/B B/A/B/B B/B/A/B Other combinations are also contemplated. A discussion of other potential therapies that may be used combination with the compounds of the present disclosure is presented elsewhere in this document. VI. Chemistry Background In some aspects, compounds of this disclosure can be synthesized using the methods of organic chemistry as described in this application. These methods can be further modified and optimized using the principles and techniques of organic chemistry as applied by a person skilled in the art. Such principles and techniques are taught, for example, in March’s Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (2007), which is incorporated by reference herein. A. Process Scale-Up The compounds utilized in methods of the disclosure described herein can be further modified and optimized for preparative, pilot- or large-scale production, either batch of continuous, using the principles and techniques of process chemistry as applied by a person skilled in the art. Such principles and techniques are taught, for example, in Practical Process Research & Development (2000), which is incorporated by reference herein. B. Chemical Definitions :KHQ^XVHG^LQ^WKH^FRQWH[W^RI^D^FKHPLFDO^JURXS^^³K\GURJHQ´^P HDQV^í+^^³K\GUR[\´^PHDQV^í2+^^ ³R[R´^PHDQV^ 2^^³FDUERQ\O´^PHDQV^í&^ 2^í^^³FDUER[\´^PHDQV^í&^ 2^2+^^DOVR^ZULWWHQ^DV^í&22+^ RU^í&22+^^^³KDOR´^PHDQV^LQGHSHQGHQWO\^í)^^í&O^^ í%U^RU^í,^^³DPLQR´^PHDQV^í1+2^^³K\GUR[\DPLQR´^ PHDQV^í1+2+^^³QLWUR´^PHDQV^í122^^ LPLQR^PHDQV^ 1+^^³F\DQR´^PHDQV^í&1^^³LVRF\DQ\O´^PHDQV^ í1 & 2^^ ³D]LGR´^ PHDQV^ í13; in a monovalent FRQWH[W^ ³SKRVSKDWH´^ PHDQV^ í23^2^^2+^2 or a GHSURWRQDWHG^IRUP^WKHUHRI^^LQ^D^GLYDOHQW^FRQWH[W^³SKRVSKDWH ´^PHDQV^í23^2^^2+^2í^RU^D^GHSURWRQDWHG^ IRUP^WKHUHRI^^³PHUFDSWR´^PHDQV^í6+^^DQG^³WKLR´^PHDQV^ 6^^³WKLRFDUERQ\O´^PHDQV^í&^ 6^í^^³VXOIRQ\O´^ PHDQV^í6^2^ ₂ í; anG^³VXOILQ\O´^PHDQV^í6^2^í^ ,Q^WKH^FRQWH[W^RI^FKHPLFDO^IRUPXODV^^WKH^V\PERO^³í´^PHDQV ^D^VLQJOH^ERQG^^³ ´^PHDQV^D^GRXEOH^ ERQG^^DQG^³Ł´^PHDQV^WULSOH^ERQG^^^7KH^V\PERO^³ ´^UHSUHVHQWV^DQ^RSWLRQDO^ERQG^^ZKLFK^LI^SUHVHQW^LV^ either single or double. 7KH^ V\PERO^³ ´ represents a single bond or a double bond. Thus, the formula covers, for example, . And it is understood that no one such ring atom forms part of more than one double bond. Furthermore, it is noted that the covalent bond symbol ³í´^^ ZKHQ^ FRQQHFWLQJ^ RQH^ RU^ WZR^ VWHUHRJHQLF^ DWRPV^^ GRHV^ QRW^ LQGLFDWH^ DQ\^ preferred stereochemistry. Instead, it covers all stereoisomers as well as mixtures thereof. The symbol ³ ´^^ZKHQ^ GUDZQ^SHUSHQGLFXODUO\^ DFURVV^ D^ ERQG (e.g., ^CH3 for methyl) indicates a point of attachment of the group. It is noted that the point of attachment is typically only identified in this manner for larger groups in order to assist the reader in unambiguously identifying a point of attachment. 7KH^V\PERO^³ ´^PHDQV^D^VLQJOH^ERQG^ZKHUH^WKH^JURXS^DWWDFKHG^WR^WKH^WKLFN ^HQG^RI^WKH^ZHGJH^LV^³RXW^ RI^WKH^SDJH^´^^7KH^V\PERO^³ ´^PHDQV^D^VLQJOH^ERQG^ZKHUH^WKH^JURXp attached to the thick end of the ZHGJH^LV^³LQWR^WKH^SDJH´^ The V\PERO^³ ´^PHDQV^D^VLQJOH^ERQG^ZKHUH^WKH^JHRPHWU\^DURXQG^D^ double bond (e.g., either E or Z) is undefined. Both options, as well as combinations thereof are therefore intended. Any undefined valency on an atom of a structure shown in this application implicitly represents a hydrogen atom bonded to that atom. A bold dot on a carbon atom indicates that the hydrogen attached to that carbon is oriented out of the plane of the paper. :KHQ^D^YDULDEOH^LV^GHSLFWHG^DV^D^³IORDWLQJ^JURXS´^RQ^D^ULQ J^V\VWHP^^IRU^H[DPSOH^^WKH^JURXS^³5´^ in the formula: , then the variable may replace any hydrogen atom attached to any of the ring atoms, including a depicted, implied, or expressly defined hydrogen, so long as a stable structure is formed. When a variable is GHSLFWHG^DV^D^³IORDWLQJ^JURXS´^RQ^D^IXVHG^ULQJ^V\VWHP^^DV^ IRU^H[DPSOH WKH^JURXS^³5´^LQ^WKH^IRUPXOD^ , then the variable may replace any hydrogen attached to any of the ring atoms of either of the fused rings unless specified otherwise. Replaceable hydrogens include depicted hydrogens (e.g., the hydrogen attached to the nitrogen in the formula above), implied hydrogens (e.g., a hydrogen of the formula above that is not shown but understood to be present), expressly defined hydrogens, and optional hydrogens whose presence depends on the identity of a ring atom (e.g., a hydrogen attached to group X, when X equals íCHí), so long as a stable structure is formed. In the example depicted, R may reside on either the 5-membered or the 6-membered ring of the fused ring system. In the formula above, the subscript OHWWHU^³\´^LPPHGLDWHO\^IROORZLQJ^WKH^5^HQFORVHG^LQ^SDUHQWK HVHV^^UHSUHVHQWV^D^QXPHULF^YDULDEOH^^^8QOHVV^ specified otherwise, this variable can be 0, 1, 2, or any integer greater than 2, only limited by the maximum number of replaceable hydrogen atoms of the ring or ring system. For the chemical groups and compound classes, the number of carbon atoms in the group or FODVV^LV^DV^LQGLFDWHG^DV^IROORZV^^³&Q´^RU^³& Q´^GHILQHV^WKH^H[DFW^QXPEHU^^Q^^RI^FDUERQ^DWRPV^LQ^WKH^ JURXS^FODVV^^^³&dQ´^defines the maximum number (n) of carbon atoms that can be in the group/class, with the minimum number as small as possible for the group/class in question. For example, it is XQGHUVWRRG^ WKDW^ WKH^PLQLPXP^ QXPEHU^ RI^ FDUERQ^ DWRPV^ LQ^ WKH^ JURXSV^ ³DON\O(Cd8)´^^ ³DONDQHGL\O(Cd8)´^^ ³KHWHURDU\O _(Cd8) ´^^ DQG^ ³DF\O _(Cd8) ´^ LV^ RQH^^ WKH^ PLQLPXP^ QXPEHU^ RI^ FDUERQ^ DWRPV^ LQ^ WKH^ JURXSV^ ³DONHQ\O _(Cd8) ´^^³DON\Q\O _(Cd8) ´^^DQG^³KHWHURF\FORDON\O _(Cd8) ´^LV^WZR^^WKH^PLQLPXP^QXPEHU^RI^FDUERQ^DWRPV^ LQ^ WKH^ JURXS^ ³F\FORDON\O(Cd8)´^ LV^ WKUHH^^ Dnd the minimum number of carbon atoms in the groups ³DU\O(Cd8)´^DQG^³DUHQHGL\O(Cd8)´^LV^VL[^^^³&Q-Qƍ´ ^GHILQHV^ERWK^WKH^PLQLPXP^^Q^^DQG^PD[LPXP^QXPEHU^^Qƍ^^ RI^FDUERQ^DWRPV^LQ^WKH^JURXS^^^7KXV^^³DON\O _(C2-10) ´^GHVLJQDWHV^WKRVH^DON\O^JURXSV^KDYLQJ^IURP^^^WR^^^ carbon atoms. These carbon number indicators may precede or follow the chemical groups or class it modifies and it may or may not be enclosed in parenthesis, without signifying any change in meaning. 7KXV^^WKH^WHUPV^³& _1-4 -DON\O´^^³&^-4-DON\O´^^³DON\O _(C1-4) ´^^DQG^³DON\O _^&^^^ ´^DUH^DOO^V\QRQ\PRXV^^^([FHSW^DV^ noted below, every carbon atom is counted to determine whether the group or compound falls with the specified number of carbon atoms. For example, the group dihexylamino is an example of a dialkylamino(C12) group; however, it is not an example of a dialkylamino(C6) group. Likewise, phenylethyl is an example of an aralkyl(C=8) group. When any of the chemical groups or compound FODVVHV^GHILQHG^KHUHLQ^LV^PRGLILHG^E\^WKH^WHUP^³VXEVWLWXWHG ´^^DQ\^FDUERQ^DWRm in the moiety replacing the hydrogen atom is not counted. Thus methoxyhexyl, which has a total of seven carbon atoms, is an example of a substituted alkyl(C1-6). Unless specified otherwise, any chemical group or compound class listed in a claim set without a carbon atom limit has a carbon atom limit of less than or equal to twelve. 7KH^WHUP^³VDWXUDWHG´^ZKHQ^XVHG^WR^PRGLI\^D^FRPSRXQG^RU^FKH PLFDO^JURXS^PHDQV^WKH^FRPSRXQG^ or chemical group has no carbon-carbon double and no carbon-carbon triple bonds, except as noted below. When the term is used to modify an atom, it means that the atom is not part of any double or triple bond. In the case of substituted versions of saturated groups, one or more carbon oxygen double bond or a carbon nitrogen double bond may be present. And when such a bond is present, then carbon- carbon double bonds that may occur as part of keto-enol tautomerism or imine/enamine tautomerism DUH^QRW^SUHFOXGHG^^^:KHQ^WKH^WHUP^³VDWXUDWHG´^LV^XVHG^WR^P RGLI\^D^VROXWLRQ^RI^D^VXEVWDQFH^^LW^PHDQs that no more of that substance can dissolve in that solution. 7KH^WHUP^³DOLSKDWLF´^VLJQLILHV^WKDW^WKH^FRPSRXQG^RU^FKHPLF DO^JURXS^VR^PRGLILHG^LV^DQ^DF\FOLF^ or cyclic, but non-aromatic compound or group. In aliphatic compounds/groups, the carbon atoms can be joined together in straight chains, branched chains, or non-aromatic rings (alicyclic). Aliphatic compounds/groups can be saturated, that is joined by single carbon-carbon bonds (alkanes/alkyl), or unsaturated, with one or more carbon-carbon double bonds (alkenes/alkenyl) or with one or more carbon-carbon triple bonds (alkynes/alkynyl). 7KH^WHUP^³DURPDWLF´^VLJQLILHV^WKDW^WKH^FRPSRXQG^RU^FKHPLFD O^JURXS^VR^PRGLILHG^KDV^D^SODQDU^ unsaturated ring of atoms with 4n +2 electrons in a fully conjugated cycliF^ʌ^V\VWHP^^ ^$Q^DURPDWLF^ compound or chemical group may be depicted as a single resonance structure; however, depiction of one resonance structure is taken to also refer to any other resonance structure. For example: Aromatic compounds may also be depicted using a circle to represent the delocalized nature of the HOHFWURQV^LQ^WKH^IXOO\^FRQMXJDWHG^F\FOLF^ʌ^V\VWHP^^WZR^QRQ- limiting examples of which are shown below: . 7KH^WHUP^³DON\O´^UHIHUV^WR^D^PRQRYDOHQW^VDWXUDWHG^DOLSKDWL F^JURXS^ZLWK^D^FDUERQ^DWRP^DV^WKH^ point of attachment, a linear or branched acyclic structure, and no atoms other than carbon and K\GURJHQ^^^7KH^JURXSV^í&+ ₃ ^0H^^^í&+ ₂ CH ₃ ^(W^^^í&+ ₂ CH ₂ CH ₃ (n-3U^RU^SURS\O^^^í&+^&+ ₃ ) ₂ (i-Pr, ⁱ 3U^RU^LVRSURS\O^^^í&+ ₂ CH ₂ CH ₂ CH ₃ (n-%X^^^í&+^&+ ₃ )CH ₂ CH ₃ (sec-EXW\O^^^í&+ ₂ CH(CH ₃ ) ₂ (isobutyl), í&^&+ ₃ ) ₃ (tert-butyl, t-butyl, t-Bu or ^t %X^^^DQG^í&+ ₂ C(CH ₃ ) ₃ (neo-pentyl) are non-limiting examples RI^DON\O^JURXSV^^^7KH^WHUP^³DONDQHGL\O´^UHIHUV^WR^D^GLYDOH QW^VDWXUDWHG^DOLSKDWLF^JURXS^^ZLWK^RQH^RU^WZR^ saturated carbon atom(s) as the point(s) of attachment, a linear or branched acyclic structure, no carbon- FDUERQ^ GRXEOH^ RU^ WULSOH^ ERQGV^^ DQG^ QR^ DWRPV^RWKHU^ WKDQ^ FDUERQ^DQG^ K\GURJHQ^^ ^7KH^ JURXSV^í&+ ₂ í ^PHWK\OHQH^^^ í&+ ₂ CH ₂ í^^ í&+ ₂ C(CH ₃ ) ₂ CH ₂ í^^ DQG^ í&+ ₂ CH ₂ CH ₂ í are non-limiting examples of DONDQHGL\O^JURXSV^^^7KH^WHUP^³DON\OLGHQH´^UHIHUV^WR^WKH^GL YDOHQW^JURXS^ &55ƍ LQ^ZKLFK^5^DQG^5ƍ^DUH^ independently hydrogen or alkyl. Non-limiting examples of alkylidene groups include: =CH ₂ , =CH(CH ₂ CH ₃ ), and =C(CH ₃ ) ₂ ^^^$Q^³DONDQH´^UHIHUV^WR^WKH^FODVV^RI^FRPSRXQGV^KDYL QJ^WKH^IRUPXOD^+í5^^ wherein R is alkyl as this term is defined above. 7KH^WHUP^³F\FORDON\O´^UHIHUV^WR^D^PRQRYDOHQW^VDWXUDWHG^DOL SKDWLF^JURXS^ZLWK^D^FDUERQ^DWRP^DV^ the point of attachment, said carbon atom forming part of one or more non-aromatic ring structures, no carbon-carbon double or triple bonds, and no atoms other than carbon and hydrogen. Non-limiting H[DPSOHV^ LQFOXGH^^í&+^&+2)2 (cyclopropyl), cyclobutyl, cyclopentyl, or cyclohexyl (Cy). As used herein, the term does not preclude the presence of one or more alkyl groups (carbon number limitation permitting) attached to a carbon atom of the non-DURPDWLF^ULQJ^VWUXFWXUH^^^7KH^WHUP^³F\FORDONDQHGL\O´^ refers to a divalent saturated aliphatic group with two carbon atoms as points of attachment, no carbon- carbon double or triple bonds, and no atoms other than carbon and hydrogen. The group is a non-OLPLWLQJ^H[DPSOH^RI^F\FORDONDQHGL\O^JURXS^^^$^³F\FORDON DQH´^UHIHUV^WR^WKH^FODVV^RI^FRPSRXQGV^ KDYLQJ^WKH^IRUPXOD^+í5^^ZKHUHLQ^5^LV^F\FORDON\O^DV^WKLV^WHU P^LV^GHILQHG^DERYH^^^ 7KH^WHUP^³DONHQ\O´^UHIHUV^WR^D^PRQRYDOHQW^XQVDturated aliphatic group with a carbon atom as the point of attachment, a linear or branched, acyclic structure, at least one nonaromatic carbon-carbon double bond, no carbon-carbon triple bonds, and no atoms other than carbon and hydrogen. Non- limiting exDPSOHV^LQFOXGH^^í&+ &+2 ^YLQ\O^^^í&+ &+&+3^^í&+ &+&+2CH3^^í&+2CH=CH2 (allyl), í&+2CH=CHCH3^^ DQG^ í&+ &+&+ &+2^^ ^ 7KH^ WHUP^ ³DONHQHGL\O´^ UHIHUV^ WR^ D^ GLYDOHQW^ XQVDWXUDWHG^ aliphatic group, with two carbon atoms as points of attachment, a linear or branched acyclic structure, at least one nonaromatic carbon-carbon double bond, no carbon-carbon triple bonds, and no atoms other WKDQ^ FDUERQ^ DQG^ K\GURJHQ^^ ^ 7KH^ JURXSV^ í&+ &+í^^ í&+ &^&+3)CH2í^^ í&+ &+&+2í, and í&+2CH=CHCH2í are non-limiting examples of alkenediyl groups. It is noted that while the alkenediyl group is aliphatic, once connected at both ends, this group is not precluded from forming SDUW^RI^DQ^DURPDWLF^VWUXFWXUH^^^7KH^WHUPV^³DONHQH´^DQG^³R OHILQ´^DUH^V\QRQ\PRXV^DQG^UHIHU^WR^WKH^FODVV^RI^ compounGV^KDYLQJ^WKH^IRUPXOD^+í5^^ZKHUHLQ^5^LV^DONHQ\O^DV^W KLV^WHUP^LV^GHILQHG^DERYH^^^6LPLODUO\^^WKH^ WHUPV^³WHUPLQDO^DONHQH´^DQG^³Į-ROHILQ´^DUH^V\QRQ\PRXV^D QG^UHIHU^WR^DQ^DONHQH^KDYLQJ^MXVW^RQH^FDUERQ- carbon double bond, wherein that bond is part of a vinyl group at an end of the molecule. 7KH^WHUP^³DON\Q\O´^UHIHUV^WR^D^PRQRYDOHQW^XQVDWXUDWHG^DOLS KDWLF^JURXS^ZLWK^D^FDUERQ^DWRP^DV^ the point of attachment, a linear or branched acyclic structure, at least one carbon-carbon triple bond, and no atoms other than carbon and hydrogen. As used herein, the term alkynyl does not preclude the presence of one or more non-aromatic carbon-FDUERQ^GRXEOH^ERQGV^^^7KH^JURXSV^í&Ł&+^^í& amp;Ł&&+ ₃ , DQG^í&+ ₂ &Ł&&+ ₃ are non-OLPLWLQJ^H[DPSOHV^RI^DON\Q\O^JURXSV^^ ^$Q^³DON\QH´^UHIHUV^WR^WKH^FODss of FRPSRXQGV^KDYLQJ^WKH^IRUPXOD^+í5^^ZKHUHLQ^5^LV^DON\Q\O^^^ 7KH^WHUP^³DU\O´^UHIHUV^WR^D^PRQRYDOHQW^XQVDWXUDWHG^DURPDWL F^JURXS^ZLWK^DQ^DURPDWLF^FDUERQ^ atom as the point of attachment, said carbon atom forming part of a one or more aromatic ring structures, each with six ring atoms that are all carbon, and wherein the group consists of no atoms other than carbon and hydrogen. If more than one ring is present, the rings may be fused or unfused. Unfused rings are connected with a covalent bond. As used herein, the term aryl does not preclude the presence of one or more alkyl groups (carbon number limitation permitting) attached to the first aromatic ring or any additional aromatic ring present. Non-limiting examples of aryl groups include phenyl (Ph), meWK\OSKHQ\O^^ ^GLPHWK\O^SKHQ\O^^ í&6H4CH2CH3 (ethylphenyl), naphthyl, and a monovalent group derived from biphenyl (e.g., 4-SKHQ\OSKHQ\O^^^^7KH^WHUP^³DUHQHGL\O´^UHIHUV^WR^D^GLYDOHQ W^DURPDWLF^JURXS^ with two aromatic carbon atoms as points of attachment, said carbon atoms forming part of one or more six-membered aromatic ring structures, each with six ring atoms that are all carbon, and wherein the divalent group consists of no atoms other than carbon and hydrogen. As used herein, the term arenediyl does not preclude the presence of one or more alkyl groups (carbon number limitation permitting) attached to the first aromatic ring or any additional aromatic ring present. If more than one ring is present, the rings may be fused or unfused. Unfused rings are connected with a covalent bond. Non- limiting examples of arenediyl groups include: . $Q^³DUHQH´^UHIHUV^WR^WKH^FODVV^RI^FRPSRXQGV^KDYLQJ^WKH^IRU PXOD^+í5^^ZKHUHLQ^5^LV^DU\O^DV^WKDW^WHUP^LV^ defined above. Benzene and toluene are non-limiting examples of arenes. 7KH^ WHUP^ ³DUDON\O´^ UHIHUV^ WR^ WKH^ PRQRYDOHQW^ JURXS^ íDONDQHGL\OíDU\O^^ LQ^ ZKLFK^ WKe terms alkanediyl and aryl are each used in a manner consistent with the definitions provided above. Non- limiting examples are: phenylmethyl (benzyl, Bn) and 2-phenyl-ethyl. 7KH^WHUP^³KHWHURDU\O´^UHIHUV^WR^D^PRQRYDOHQW^DURPDWLF^JURX S^ZLWK^DQ^DURPDWLF^Farbon atom or nitrogen atom as the point of attachment, said carbon atom or nitrogen atom forming part of one or more aromatic ring structures, each with three to eight ring atoms, wherein at least one of the ring atoms of the aromatic ring structure(s) is nitrogen, oxygen or sulfur, and wherein the heteroaryl group consists of no atoms other than carbon, hydrogen, aromatic nitrogen, aromatic oxygen and aromatic sulfur. If more than one ring is present, the rings are fused; however, the term heteroaryl does not preclude the presence of one or more alkyl or aryl groups (carbon number limitation permitting) attached to one or more ring atoms. Non-limiting examples of heteroaryl groups include benzoxazolyl, benzimidazolyl, furanyl, imidazolyl (Im), indolyl, indazolyl, isoxazolyl, methylpyridinyl, oxazolyl, oxadiazolyl, phenylpyridinyl, pyridinyl (pyridyl), pyrrolyl, pyrimidinyl, pyrazinyl, quinolyl, quinazolyl, TXLQR[DOLQ\O^^WULD]LQ\O^^WHWUD]RO\O^^WKLD]RO\O^^WKLHQ\O^^DQG ^WULD]RO\O^^^7KH^WHUP^³N-KHWHURDU\O´^UHIers to a KHWHURDU\O^JURXS^ZLWK^D^QLWURJHQ^DWRP^DV^WKH^SRLQW^RI^DWWDFK PHQW^^^$^³KHWHURDUHQH´^UHIHUV^WR^WKH^FODVV^RI^ FRPSRXQGV^KDYLQJ^WKH^IRUPXOD^+í5^^ZKHUHLQ^5^LV^KHWHURDU\O^^ ^3\ULGLQH^DQG^TXLQROLQH^DUH^QRQ-limiting examples of heteroarenes. 7KH^WHUP^³KHWHURDUDON\O´^UHIHUV^WR^WKH^PRQRYDOHQW^JURXS^í DONDQHGL\OíKHWHURDU\O^^LQ^ZKLFK^WKH^ terms alkanediyl and heteroaryl are each used in a manner consistent with the definitions provided above. Non-limiting examples are: pyridinylmethyl and 2-quinolinyl-ethyl. 7KH^WHUP^³KHWHURF\FORDON\O´^UHIHUV^WR^D^PRQRYDOHQW^QRQ-aro matic group with a carbon atom or nitrogen atom as the point of attachment, said carbon atom or nitrogen atom forming part of one or more non-aromatic ring structures, each with three to eight ring atoms, wherein at least one of the ring atoms of the non-aromatic ring structure(s) is nitrogen, oxygen or sulfur, and wherein the heterocycloalkyl group consists of no atoms other than carbon, hydrogen, nitrogen, oxygen and sulfur. If more than one ring is present, the rings are fused. As used herein, the term does not preclude the presence of one or more alkyl groups (carbon number limitation permitting) attached to one or more ring atoms. Also, the term does not preclude the presence of one or more double bonds in the ring or ring system, provided that the resulting group remains non-aromatic. Non-limiting examples of heterocycloalkyl groups include aziridinyl, azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, tetrahydrofuranyl, tetrahydrothiofuranyl, tetrahydropyranyl, pyranyl, R[LUDQ\O^^ DQG^ R[HWDQ\O^^ ^ 7KH^ WHUP^ ³N-KHWHURF\FORDON\O´^ UHIHUV^ WR^ D^ KHWHURF\FORDON\O^ JURXS^ ZLWK^ D^ nitrogen atom as the point of attachment. N-pyrrolidinyl is an example of such a group. The terP^³KHWHURF\FORDONDON\O´^UHIHUV^WR^WKH^PRQRYDOHQW^JURXS^ íDONDQHGL\OíKHWHURF\FORDON\O^^ in which the terms alkanediyl and heterocycloalkyl are each used in a manner consistent with the definitions provided above. Non-limiting examples are: morpholinylmethyl and piperidinylethyl. 7KH^WHUP^³DF\O´^UHIHUV^WR^WKH^JURXS^í&^2^5^^LQ^ZKLFK^ 5^LV^D^K\GURJHQ^^DON\O^^F\FORDON\O^^RU^ DU\O^DV^WKRVH^WHUPV^DUH^GHILQHG^DERYH^^ ^7KH^JURXSV^^í&+2^^í&^2^&+3 ^DFHW\O^^$F^^^í&^2^&+2CH3, í&^2^&+^&+3)2^^í&^2^&+^&+2)2^^í&a mp;^2^&6H5^^DQG^íC(O)C6H4CH3 are non-limiting examples of acyl JURXSV^^ ^$^³WKLRDF\O´^ LV^GHILQHG^ LQ^DQ^DQDORJRXV^PDQQHU^^H[FHSW^WKDW^WKH^R[\JHQ^DWRP^RI^WKH^J URXS^ í&^2^5^KDV^EHHQ^UHSODFHG^ZLWK^D^VXOIXU^DWRP^^í&^6^ 5^^^7KH^WHUP^³DOGHK\GH´^FRUUHVSRQGV^WR^DQ^DON\O^ group, as defiQHG^DERYH^^DWWDFKHG^WR^D^í&+2^JURXS^^^ 7KH^WHUP^³DONR[\´^UHIHUV^ WR^ WKH^JURXS^í25^^ LQ^ZKLFK^5^LV^DQ^DON\O^^ DV^ WKDW^ WHUP^LV^GHILQHG^ above. Non-OLPLWLQJ^ H[DPSOHV^ LQFOXGH^^ í2&+3 ^PHWKR[\^^^ í2&+2CH3 ^HWKR[\^^^ í2&+2CH2CH3, í2&+^&+3)2 ^LVRSURSR[\^^^ RU^ í2&^&+3)3 (tert-EXWR[\^^^ ^ 7KH^ WHUPV^ ³F\FORDONR[\´^^ ³DONHQ\OR[\´^^ ³DON\Q\OR[\´^^³DU\OR[\´^^³DUDONR[\´^^³KHWHURDU\OR[\´ ^^³KHWHURF\FORDONR[\´^^DQG^³DF\OR[\´^^ZKHQ^XVHG^ ZLWKRXW^WKH^³VXEVWLWXWHG´^PRGLILHU^^UHIHUV^WR^JURXSV^^GHIL QHG^DV^í25^^LQ^ZKLFK^5^LV^F\FORDON\O^^DONHQyl, DON\Q\O^^DU\O^^DUDON\O^^KHWHURDU\O^^KHWHURF\FORDON\O^^DQG^DF \O^^UHVSHFWLYHO\^^ ^7KH^WHUP^³DON\OWKLR´^DQG^ ³DF\OWKLR´^UHIHUV^WR^WKH^JURXS^í65^^LQ^ZKLFK^5^LV^DQ^DON\ O^DQG^DF\O^^UHVSHFWLYHO\^^^7KH^WHUP^³DOFRKRO´^ corresponds to an alkane, as defined above, wherein at least one of the hydrogen atoms has been UHSODFHG^ZLWK^D^K\GUR[\^JURXS^^^7KH^WHUP^³HWKHU´^FRUUHVSRQ GV^WR^DQ^DONDQH^^DV^GHILQHG^DERYH^^ZKHUHLQ^ at least one of the hydrogen atoms has been replaced with an alkoxy group. 7KH^WHUP^³DON\ODPLQR´^UHIHUV^WR^WKH^JURXS^í1+5^^LQ^ZKLFK^ 5^LV^DQ^DON\O^^DV^WKDW^WHUP^LV^GHILQHG^ above. Non-OLPLWLQJ^H[DPSOHV^LQFOXGH^^í1+&+ ₃ DQG^í1+&+ ₂ CH ₃ ^^^7KH^WHUP^³GLDON\ODPLQR´^UHIHUV^ WR^ WKH^ JURXS^ í155ƍ^^ LQ^ZKLFK^5^ DQG^5ƍ^ FDQ^ EH^ WKH^ VDPH^ RU^ GLIIHUHQW^ DON\O^ JURXSV^^ ^ 1RQ-limiting H[DPSOHV^ RI^ GLDON\ODPLQR^ JURXSV^ LQFOXGH^^ í1^&+ ₃ ) ₂ DQG^ í1^&+ ₃ )(CH ₂ CH ₃ ^^^ ^ 7KH^ WHUP^ ³DPLGR´^ ^DF\ODPLQR^^^ZKHQ^XVHG^ZLWKRXW^WKH^³VXEVWLWXWHG´^PRGLILHU^ ^UHIHUV^WR^WKH^JURXS^í1+5^^LQ^ZKLFK^5^LV^ acyl, as that term is defined above. A non-limiting example of an DPLGR^JURXS^LV^í1+&^2^&+ ₃ . :KHQ^D^FKHPLFDO^JURXS^LV^XVHG^ZLWK^WKH^³VXEVWLWXWHG´^PRGLI LHU^^RQH^RU^PRUH^K\GURJHQ^DWRP^ KDV^EHHQ^UHSODFHG^^LQGHSHQGHQWO\^DW^HDFK^LQVWDQFH^^E\^í2+^^ í)^^í&O^^í%U^^í,^^í1+ ₂ ^^í12 ₂ ^^í&2 ₂ H, íCO ₂ CH ₃ ^^ í&2 ₂ CH ₂ CH ₃ ^^ í&1^^ í6+^^ í2&+ ₃ , íOCH ₂ CH ₃ ^^ í&^2^&+ ₃ ^^ í1+&+ ₃ ^^ í1+&+ ₂ CH ₃ , í1^&+ ₃ ) ₂ ^^ í&^2^1+ ₂ ^^ í&^2^1+&+ ₃ ^^ í&^2^1^&+ ₃ ) ₂ ^^ í2&^2^&+ ₃ ^^ í1+&^2^&+ ₃ ^^ í6^2^ ₂ OH, or í6^2^ ₂ NH ₂ . For example, the following groups are non-limiting examples of substituted alkyl groups: í&+ ₂ 2+^^í&+ ₂ &O^^í&) ₃ ^^í&+ ₂ &1^^í&+ ₂ &^2^2+^^í&+ ₂ C(O)OCH ₃ ^^í&+ ₂ C(O)NH ₂ ^^í&+ ₂ C(O)CH ₃ , í&+ ₂ OCH ₃ ^^í&+ ₂ OC(O)CH ₃ ^^í&+ ₂ NH ₂ ^^í&+ ₂ N(CH ₃ ) ₂ ^^DQG^í&+ ₂ CH ₂ &O^^^7KH^WHUP^³KDORDON\O´^LV^D^ subset of substituted alkyl, in which the hydrogen atom replacement is limited to halo (i.e. í)^^í&O^^ í%U^^RU^í,^^VXFK^WKDW^QR^RWKHU^DWRPV^DVLGH^IURP^FDUERQ^^K\ GURJHQ^DQG^KDORJHQ^DUH^SUHVHQW^^^7KH^JURXS^^ í&+2Cl is a non-OLPLWLQJ^H[DPSOH^RI^D^KDORDON\O^^ ^7KH^ WHUP^³IOXRURDON\O´^ LV^D^VXEVHW^RI^VXEVWLWXWHG^ alkyl, in which the hydrogen atom replacement is limited to fluoro such that no other atoms aside from FDUERQ^^K\GURJHQ^DQG^IOXRULQH^DUH^SUHVHQW^^^7KH^JURXSV^í&am p;+2)^^í&)3^^DQG^í&+2CF3 are non-limiting examples of fluoroalkyl groups. Non-limiting examples of substituted aralkyls are: (3-chlorophenyl)- methyl, and 2-chloro-2-phenyl-eth-1-\O^^ ^ 7KH^ JURXSV^^ í&^2^&+2CF3^^ í&22+^ ^FDUER[\O^^^ í&22CH3 ^PHWK\OFDUER[\O^^^ í&22CH2CH3^^ í&^2^1+2 ^FDUEDPR\O^^^ DQG^ í&21^&+3)2, are non-limiting H[DPSOHV^ RI^ VXEVWLWXWHG^ DF\O^ JURXSV^^ ^ 7KH^ JURXSV^ í1+&^2^2&+3 DQG^ í1+&^2^1+&+3 are non- limiting examples of substituted amido groups. 7KURXJKRXW^ WKLV^ DSSOLFDWLRQ^^ WKH^ WHUP^ ³DERXW´^ LV^ XVHG^ WR^ LQGLFDWH^ WKDW^ D^ YDOXH^ LQFOXGHV^ WKH^ inherent variation of error for the device, the method being employed to determine the value, or the YDULDWLRQ^WKDW^H[LVWV^DPRQJ^WKH^VWXG\^VXEMHFWV^RU^SDWLHQWV^^ ^8QOHVV^RWKHUZLVH^QRWHG^^WKH^WHUP^³DERXW´^LV^ used to indicate a value of ±10% of the reported value, preferably a value of ±5% of the reported value. It is to be understood that, whenever the terP^³DERXW´^LV^XVHG^^D^VSHFLILF^UHIHUHQFH^WR^WKH^H[DFW^ QXPHULFDO^YDOXH^LQGLFDWHG^LV^DOVR^LQFOXGHG^´ $Q^³DFWLYH^LQJUHGLHQW´^^$,^^RU^DFWLYH^SKDUPDFHXWLFDO^LQJUH GLHQW^^$3,^^^DOVR^UHIHUUHG^WR^DV^DQ^ active compound, active substance, active agent, pharmaceutical agent, agent, biologically active molecule, or a therapeutic compound) is the ingredient in a pharmaceutical drug that is biologically active. 7KH^WHUPV^³FRPSULVH^´^³KDYH´^DQG^³LQFOXGH´^DUH^RSHQ-en ded linking verbs. Any forms or tenses of one or more of WKHVH^YHUEV^^ VXFK^DV^³FRPSULVHV^´^³FRPSULVLQJ^´^³KDV^´^³KDYLQJ^´^ ³LQFOXGHV´^DQG^ ³LQFOXGLQJ^´^DUH^DOVR^RSHQ-HQGHG^^^)RU^H[DPSOH^^DQ\^PHWKRG ^WKDW^³FRPSULVHV^´^³KDV´^RU^³LQFOXGHV´^RQH^ or more steps is not limited to possessing only those one or more steps and also covers other unlisted steps. 7KH^WHUP^³HIIHFWLYH^´^DV^WKDW^WHUP^LV^XVHG^LQ^WKH^VSHFLILF DWLRQ^DQG^RU^FODLPV^^PHDQV^DGHTXDWH^WR^ DFFRPSOLVK^ D^ GHVLUHG^^ H[SHFWHG^^ RU^ LQWHQGHG^ UHVXOW^^ ^ ³(IIHFWLYH^ DPRXQW^´^ ³7KHUDSHXWLFDOO\^ HIIHFWLYH^ DPRXQW´^RU^³SKDUPDFHXWLFDOO\^HIIHFWLYH^DPRXQW´^ZKHQ^XVHG^ LQ^WKH^FRQWH[W^RI^WUHDWLQJ^D^SDWLHQW^RU^VXEMHFW^ with a compound means that amount of the compound which, when administered to the patient or subject, is sufficient to effect such treatment or prevention of the disease as those terms are defined below. $Q^³H[FLSLHQW´ is a pharmaceutically acceptable substance formulated along with the active ingredient(s) of a medication, pharmaceutical composition, formulation, or drug delivery system. Excipients may be used, for example, to stabilize the composition, to bulk up the composition (thus RIWHQ^UHIHUUHG^WR^DV^³EXONLQJ^DJHQWV^´^³ILOOHUV^´^RU^³G LOXHQWV´^ZKHQ^XVHG^IRU^WKLV^SXUSRVH^^^RU^WR^FRQIHU^D^ therapeutic enhancement on the active ingredient in the final dosage form, such as facilitating drug absorption, reducing viscosity, or enhancing solubility. Excipients include pharmaceutically acceptable versions of antiadherents, binders, coatings, colors, disintegrants, flavors, glidants, lubricants, preservatives, sorbents, sweeteners, and vehicles. The main excipient that serves as a medium for conveying the active ingredient is usually called the vehicle. Excipients may also be used in the manufacturing process, for example, to aid in the handling of the active substance, such as by facilitating powder flowability or non-stick properties, in addition to aiding in vitro stability such as prevention of denaturation or aggregation over the expected shelf life. The suitability of an excipient will typically vary depending on the route of administration, the dosage form, the active ingredient, as well as other factors. $Q^³LVRPHU´^RI^D^ILUVW^FRPSRXQG^LV^D^VHSDUDWH^FRPSRXQG^LQ^ ZKLFK^HDFK^PROHFXOH^FRQWDLQV^WKH^ same constituent atoms as the first compound, but where the configuration of those atoms in three dimensions differs. $V^JHQHUDOO\^XVHG^KHUHLQ^³SKDUPDFHXWLFDOO\^DFFHSWDEOH´^UHI HUV^WR^WKRVH^FRPSRXQGV^^PDWHULDOV^^ compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues, organs, and/or bodily fluids of human beings and animals without excessive toxicity, irritation, allergic response, or other problems or complications commensurate with a reasonable benefit/risk ratio. ³3KDUPDFHXWLFDOO\^ DFFHSWDEOH^ VDOWV´^PHans salts of compounds disclosed herein which are pharmaceutically acceptable, as defined above, and which possess the desired pharmacological activity. Such salts include acid addition salts formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; or with organic acids such as 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, 2-naphthalenesulfonic acid, 3-SKHQ\OSURSLRQLF^ DFLG^^ ^^^ƍ-methylenebis(3-hydroxy-2-ene-1-carboxylic acid), 4-methylbicyclo[2.2.2]oct-2-ene-1-carboxylic acid, acetic acid, aliphatic mono- and dicarboxylic acids, aliphatic sulfuric acids, aromatic sulfuric acids, benzenesulfonic acid, benzoic acid, camphorsulfonic acid, carbonic acid, cinnamic acid, citric acid, cyclopentanepropionic acid, ethanesulfonic acid, fumaric acid, glucoheptonic acid, gluconic acid, glutamic acid, glycolic acid, heptanoic acid, hexanoic acid, hydroxynaphthoic acid, lactic acid, laurylsulfuric acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, muconic acid, o-(4-hydroxybenzoyl)benzoic acid, oxalic acid, p-chlorobenzenesulfonic acid, phenyl-substituted alkanoic acids, propionic acid, p-toluenesulfonic acid, pyruvic acid, salicylic acid, stearic acid, succinic acid, tartaric acid, tertiarybutylacetic acid, trimethylacetic acid, and the like. Pharmaceutically acceptable salts also include base addition salts which may be formed when acidic protons present are capable of reacting with inorganic or organic bases. Acceptable inorganic bases include sodium hydroxide, sodium carbonate, potassium hydroxide, aluminum hydroxide and calcium hydroxide. Acceptable organic bases include ethanolamine, diethanolamine, triethanolamine, tromethamine, N-methylglucamine and the like. It should be recognized that the particular anion or cation forming a part of any salt of this invention is not critical, so long as the salt, as a whole, is pharmacologically acceptable. Additional examples of pharmaceutically acceptable salts and their methods of preparation and use are presented in Handbook of Pharmaceutical Salts: Properties, and Use (P. H. Stahl & C. G. Wermuth eds., Verlag Helvetica Chimica Acta, 2002). $^ ³SKDUPDFHXWLFDOO\^ DFFHSWDEOH^ FDUULHU^´^ ³GUXJ^ FDUULHU^´^ RU^ VLPSO\^ ³FDUULHU´^ LV^ D^ pharmaceutically acceptable substance formulated along with the active ingredient medication that is involved in carrying, delivering and/or transporting a chemical agent. Drug carriers may be used to improve the delivery and the effectiveness of drugs, including for example, controlled-release technology to modulate drug bioavailability, decrease drug metabolism, and/or reduce drug toxicity. Some drug carriers may increase the effectiveness of drug delivery to the specific target sites. Examples of carriers include: liposomes, microspheres (e.g., made of poly(lactic-co-glycolic) acid), albumin microspheres, synthetic polymers, nanofibers, protein-DNA complexes, protein conjugates, erythrocytes, virosomes, and dendrimers. $^³SKDUPDFHXWLFDO^ GUXJ´^ ^DOVR^ UHIHUUHG^ WR^ DV^ D^ SKDUPDFHXWLFDO^^ SKDUPDFHXWLFDO^ SUHSDUDWLRQ^^ pharmaceutical composition, pharmaceutical formulation, pharmaceutical product, medicinal product, medicine, medication, medicament, or simply a drug, agent, or preparation) is a composition used to diagnose, cure, treat, or prevent disease, which comprises an active pharmaceutical ingredient (API) (defined above) and optionally contains one or more inactive ingredients, which are also referred to as excipients (defined above). ³3URGUXJ´^ means a compound that is convertible in vivo metabolically into an active pharmaceutical ingredient of the present invention. The prodrug itself may or may not have activity with in its prodrug form. For example, a compound comprising a hydroxy group may be administered as an ester that is converted by hydrolysis in vivo to the hydroxy compound. Non-limiting examples of suitable esters that may be converted in vivo into hydroxy compounds include acetates, citrates, lactates, phosphates, tartrates, malonates, oxalates, salicylates, propionates, succinates, fumarates, maleates, methylene-bis-E-hydroxynaphthoate, gentisates, isethionates, di-p-toluoyltartrates, methanesulfonates, ethanesulfonates, benzenesulfonates, p-toluenesulfonates, cyclohexylsulfamates, quinates, and esters of amino acids. Similarly, a compound comprising an amine group may be administered as an amide that is converted by hydrolysis in vivo to the amine compound. $^³VWHUHRLVRPHU´^RU^³RSWLFDO^ LVRPHU´^ LV^DQ^ LVRPHU^RI^D^JLYHQ^FRPSRXQG^LQ^ZKLFK^ WKH^VDPH^ atoms are bonded to the same other atoms, but where the configuration of those atoms in three GLPHQVLRQV^GLIIHUV^^^³(QDQWLRPHUV´^DUH^VWHUHRLVRPHUV^RI^D^ JLYHQ^FRPSRXQG^WKDW^DUH^PLUURU^LPDJHV^RI^ HDFK^RWKHU^^OLNH^OHIW^DQG^ULJKW^KDQGV^^^³'LDVWHUHRPHUV´^DU H^VWHUHRLVRPHUV^RI^D^JLYHQ^FRPSRXnd that are not enantiomers. Chiral molecules contain a chiral center, also referred to as a stereocenter or stereogenic center, which is any point, though not necessarily an atom, in a molecule bearing groups such that an interchanging of any two groups leads to a stereoisomer. In organic compounds, the chiral center is typically a carbon, phosphorus or sulfur atom, though it is also possible for other atoms to be stereocenters in organic and inorganic compounds. A molecule can have multiple stereocenters, giving it many stereoisomers. In compounds whose stereoisomerism is due to tetrahedral stereogenic centers (e.g., tetrahedral carbon), the total number of hypothetically possible stereoisomers will not exceed 2 ⁿ , where n is the number of tetrahedral stereocenters. Molecules with symmetry frequently have fewer than the maximum possible number of stereoisomers. A 50:50 mixture of enantiomers is referred to as a racemic mixture. Alternatively, a mixture of enantiomers can be enantiomerically enriched so that one enantiomer is present in an amount greater than 50%. Typically, enantiomers and/or diastereomers can be resolved or separated using techniques known in the art. It is contemplated that that for any stereocenter or axis of chirality for which stereochemistry has not been defined, that stereocenter or axis of chirality can be present in its R form, S form, or as a mixture of the R and S forms, including racemic and non-racemic mixtures. As used KHUHLQ^^ WKH^SKUDVH^³VXEVWDQWLDOO\^IUHH^IURP^RWKHU^VWHUHRLVRPHUV´^ PHDQV^WKDW^WKH^FRPSRVLWLRQ^FRQWDLQV^^ ^^^^^PRUH^SUHIHUDEO\^^ ^^^^^HYHQ^PRUH^SUHIHUDEO\^^ 5%, or PRVW^SUHIHUDEO\^^ 1% of another stereoisomer(s). 7KH^WHUP^³XQLW^GRVH´^UHIHUV^ WR^D^ IRUPXODWLRQ^RI^WKH^FRPSRXQG^RU^FRPSRVLWLRQ^VXFK^ WKDW^ WKH^ formulation is prepared in a manner sufficient to provide a single therapeutically effective dose of the active ingredient to a patient in a single administration. Such unit dose formulations that may be used include but are not limited to a single tablet, capsule, or other oral formulations, or a single vial with a syringeable liquid or other injectable formulations. The terms "a" or "an," as used in herein means one or more. In addition, the phrase "substituted with a[n]," as used herein, means the specified group may be substituted with one or more of any or all of the named substituents. 7KH^ WHUPV^ ³WUHDWLQJ´^ RU^ ³WUHDWPHQW´^ UHIHUV^ WR^ DQ\^ LQGLFLD^ RI^ VXFFHVV^ LQ^ WKH^ WUHDWPHQW^ RU^ amelioration of an injury, disease, pathology or condition, including any objective or subjective parameter such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; improving a patient’s physical or mental well-being. The treatment or amelioration of symptoms can be based on objective or subjective parameters, including the results of a physical examination, neuropsychiatric exams, and/or a psychiatric evaluation. For example, the certain methods presented herein successfully treat a disease associated with a neurological or neurodegenerative disorder. The term "treating" and conjugations thereof, include prevention of an injury, pathology, condition, or disease. 7KH^WHUP^³SUHYHQWLQJ´^RU^³SUHYHQWLRQ´^UHIHUV^WR^DQ\^LQGL FLD^RI^VXFFHVV^LQ^SURWHFWLQJ^D^VXEMHFW^ or patient (e.g., a subject or patient at risk of developing a disease or condition) from developing, contracting, or having a disease or condition (e.g., a neurological disease), including preventing one or more symptoms of a disease or condition or diminishing the occurrence, severity, or duration of any symptoms of a disease or condition following administration of a prophylactic or preventative composition as described herein. ³&RQWURO´^RU^³FRQWURO^H[SHULPHQW´^LV^XVHG^LQ^DFFRUGD QFH^ZLWK^LWV^SODLQ^RUGLQDU\^PHDQLQJ^DQG^ refers to an experiment in which the subjects or reagents of the experiment are treated as in a parallel experiment except for omission of a procedure, reagent, or variable of the experiment. In some instances, the control is used as a standard of comparison in evaluating experimental effects. In some embodiments, a control is the measurement of infection or one or more symptoms of infection in the absence of a composition as described herein (including embodiments). ³&RQWDFWLQJ´^LV^XVHG^LQ^DFFRUGDQFH^ZLWK^LWV^SODLQ^RUGL QDU\^PHDQLng and refers to the process of allowing at least two distinct species (e.g., compositions, compounds, bacterium, virus, biomolecules, or cells) to become sufficiently proximal to react, interact or physically touch. It should be appreciated; however, the resulting reaction product can be produced directly from a reaction between the added reagents or from an intermediate from one or more of the added reagents which can be produced in the reaction mixture. 7KH^WHUP^³FRQWDFWLQJ´^PD\^LQFOXGH^DOORZLQJ^WZR^VSHcies to react, interact, or physically touch, wherein the two species may be a compound, composition, cell, virus, virus particle, protein, enzyme, or patient. In some embodiments, contacting includes allowing a compound described herein to interact with a cell that is involved in a signaling pathway. In some embodiments, contacting includes allowing a compound described herein to interact with a component of a subject’s neurological system wherein calcium signaling pathways are involved. As defined hereLQ^^WKH^WHUP^³LQKLELWLRQ´^^³LQKLELW´^^³LQKLELWLQJ´ ^DQG^WKH^OLNH^LQ^UHIHUHQFH^WR^D^ protein-inhibitor or interaction means negatively affecting (e.g., decreasing) the activity or function of the protein. In some embodiments, inhibition refers to reduction of a disease or symptoms of disease. In some embodiments, inhibition refers to a reduction in the activity of a signal transduction pathway or signaling pathway. Thus, inhibition includes, at least in part, partially or totally blocking stimulation, decreasing, preventing, or delaying activation, or inactivating, desensitizing, or down-regulating the signaling pathway. 7KH^WHUP^³PRGXODWH´^LV^XVHG^LQ^DFFRUGDQFH^ZLWK^LWV^SODLQ^R UGLQDU\^PHDQLQJ^DQG^UHIHUV^WR^WKH^DFW^ of changing or varying one or more propertiHV^^ ³0RGXODWLRQ´^ UHIHUV^ WR^ WKH^ SURFHVV^ RI^ FKDQJLQJ^ RU^ varying one or more properties. For example, as applied to the effects of a modulator on a target, to modulate means to change by increasing or decreasing a property or function of the target or the amount of the target. ³3DWLHQW´^UHIHUV^WR^D^OLYLQJ^RUJDQLVP^VXIIHULQJ^IURP^RU^SU RQH^WR^D^GLVHDVH^RU^FRQGLWLRQ^WKDW^FDQ^ be treated by administration of a composition as provided herein. Non-limiting examples include humans, other mammals, bovines, rats, mice, dogs, monkeys, goat, sheep, cows, deer, and other non-mammalian animals. In some embodiments, a patient is human. In some embodiments, a patient or subject in need thereof, refers to a living organism (e.g., human) at risk of developing, contracting, or having a disease or condition associated with neurodegeneration. ³'LVHDVH´^RU^³FRQGLWLRQ´^UHIHU^WR^D^VWDWH^RI^EHLQJ^RU^KH DOWK^VWDWXV^RI^D^SDWLHQW^RU^VXEMHFW^FDSDEOH^ of being treated with the methods provided herein. In some embodiments, the disease is a disease related to dysregulation of calcium signaling. The term "preparation" is intended to include the formulation of the active compound with encapsulating material as a carrier providing a capsule in which the active component with or without other carriers, is surrounded by a carrier, which is thus in association with it. As used herein, the term "administering" means oral administration, administration as a suppository, topical contact, intravenous, intraperitoneal, intramuscular, intralesional, intrathecal, intranasal, intradermal, mucosal, intrarectal, intravaginal, topical, transcutaneous, or subcutaneous administration. Administration is by any route, including parenteral and transmucosal (e.g., buccal, sublingual, palatal, gingival, nasal, vaginal, rectal, or transdermal). Parenteral administration includes, e.g., intravenous, intramuscular, intra-arteriole, intradermal, subcutaneous, intraperitoneal, intraventricular, and intracranial. Other modes of delivery include, but are not limited to, the use of liposomal formulations, intravenous infusion, transdermal patches, etc. By "co-administer" it is meant that a composition described herein is administered at the same time, just prior to, or just after the administration of one or more additional therapies. The compositions utilized in methods of the disclosure can be administered alone or can be coadministered to the patient. Coadministration is meant to include simultaneous or sequential administration of the compounds individually or in combination (more than one composition). Thus, the preparations can also be combined, when desired, with other active substances. The compositions utilized in methods of the disclosure can be delivered by transdermally, by a topical route, transcutaneously, formulated as solutions, suspensions, emulsions, gels, creams, ointments, pastes, jellies, paints, powders, and aerosols. 7KH^WHUPV^³GRVH´^DQG^³GRVDJH´^DUH^XVHG^LQWHUFKDQJHDEO\^K HUHLQ^^^$^GRVH^UHIHUV^WR^WKH^DPRXQW^ of active ingredient given to an individual at each administration. For the present methods and compositions utilized in methods of the disclosure, the dose may generally refer to the amount of disease treatment. The dose will vary depending on a number of factors, including the range of normal doses for a given therapy, frequency of administration; size and tolerance of the individual; severity of the condition; risk of side effects; and the route of administration. One of skill will recognize that the dose can be modified GHSHQGLQJ^RQ^WKH^DERYH^IDFWRUV^RU^EDVHG^RQ^WKHUDSHXWLF^SURJU HVV^^^7KH^WHUP^³GRVDJH^ IRUP´^UHIHUV^WR^WKH^SDUWLFXODU^IRUPDW^RI^WKH^SKDUPDFHXWLFDO ^RU^SKDUPDFHXWLFDO^FRPSRVLWLRQ^DQG^GHSHQGV^ on the route of administration. For example, a dosage form can be in a liquid form for nebulization, e.g., for inhalants, in a tablet or liquid, e.g., for oral delivery, or a saline solution, e.g., for injection. 7KH^ WHUP^ ³DVVRFLDWHG´^ RU^ ³DVVRFLDWHG^ ZLWK´^ DV^ XVHG^ KHUHLQ^ WR^ GHVFULEH^ D^ GLVHDVH^ ^e.g., a neurological disesase) means that the disease is caused by, or a symptom of the disease is caused by, what is described as disease associated or what is described as associated with the disease. As used herein, what is described as being associated with a disease, if a causative agent, could be a target for treatment of the disease. The above definitions supersede any conflicting definition in any reference that is incorporated by reference herein. The fact that certain terms are defined, however, should not be considered as indicative that any term that is undefined is indefinite. Rather, all terms used are believed to describe the invention in terms such that one of ordinary skill can appreciate the scope and practice the present invention. VII. Examples The following examples are included to demonstrate preferred embodiments of the disclosure. It should be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function well in the practice of the disclosure, and thus can be considered to constitute preferred modes for its practice. However, those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit and scope of the disclosure. EXAMPLE 1 – Inducing Intercellular Calcium Waves in HEK293 Cells Molecular motors (MM) employed in this study have overcrowded alkene motors based on the primary design by Feringa et al (Klok et al., 2008). Their typical structure consists of a rotor connected to a stator by an atropisomeric alkene. When these MM are excited by incident photons, the rotor rotates unidirectionally relative to the stator, undergoing two photoisomerization steps and two thermal helix inversions before returning to the starting position (FIG.1A) (Klok et al., 2008). Overcrowded alkene motors locomote in solution (García-López et al., 2015), drill through synthetic lipid bilayers and cell membranes following light activation (García-López et al., 2017), and have previously been used to exert mechanical forces on individual cell-surface receptors via antibody targeting (Zheng et al., 2021). Here, the cellular responses to MM administered directly to cells were studied without the use of chemical targeting or extracellular scaffolds, which facilitates their use in vivo.7KH^PRLHW\^³;´^LQ^FIG. 1A can be interchanged to modulate MM rotation rate, which is determined by the favorability of the thermal helix inversion step (García-López et al., 2020; Pollard et al., 2007). To investigate cellular responses to the actuation of MM, live-cell calcium tracking were employed. HEK293 cells were treated with the fluorescent intracellular calcium indicator Fluo-4 and loaded with MM. The structures of the MM employed in this study are shown in FIG. 1B, and the calcium responses of cells treated with fast-rotating MM 1 are shown in FIG. 1C. Stimulation of a single MM 1-treated cell with a 400 nm laser (3.2×10 ² W cm ^-2 ) increased Fluo-4 fluorescence in the targeted cell, reflecting a spike in the intracellular calcium concentration similar to that observed when cells are mechanically perturbed with a micropipette (Leybaert & Sanderson, 2012; Sanderson et al., 1990). In the presence of the vehicle only, no calcium responses were evoked by the same laser treatment (FIG.2). Calcium responses were observed to propagate to adjacent cells (FIG.3) according to the degree of electrical connectivity between individual colonies. Similar responses were observed when cells were treated with scavengers of reactive oxygen species (ROS, FIG.4) and in experiments using X-Rhod-1 in place of Fluo-4 (FIG. 5), suggesting that the observed responses do not depend on the production of ROS or fluorescence resonant energy transfer interactions between MM 1 and calcium tracking dyes. Cellular responses to MM were repeatable (FIG.6), and their amplitude could be controlled by the intensity of incident light (FIG. 7). The strength of the evoked response also determines the downstream effects of stimulation. At typical stimulation irradiances (3.2×10 ² W cm ^-2 for 250 ms), cells recovered from stimulation and showed no signs of apoptosis or necrosis (see FIGS. 8 & 9). Cells stimulated at higher intensities (6.4×10 ² W cm ^-2 for 4 s) showed membrane blebbing and calcium accumulation over a 30 min period, indicating cell death (FIG. 10) (Kepp et al., 2011). Hence, MM- induced ICW can be tuned between physiological, supraphysiological, and pathophysiological response regimes by adjusting the stimulus intensity (Leybaert & Sanderson, 2012). Calcium responses induced by MM 1 actuation were also observed in other cell lines, including neuroblast (N2A; FIG. 11) and HeLa cells (FIG.12). The calcium responses elicited by a library of MM were investigated consisting of two fast- rotating motors (MM 1-2) and two complementary motors (MM 3-4) used to test the effects of rotation speed and directionality (FIG.1B). MM 1 was synthesized with a six-membered ring stator containing a central sulfur atom and rotates unidirectionally at ~3 MHz, mimicking designs previously shown to kill cancer cells and antibiotic-resistant bacteria (Galbadage et al., 2019; Santos et al., 2022; Alaya- Orozco et al., 2020). MM 2 and MM 3 are chemically similar to MM 1 but rotate at different rates. MM 2, which rotates at ~43 Hz, was synthesized with a six-member ring stator with two methyl groups branching off the center carbon atom (Pollard et al., 2007). MM 3, a slow-rotating motor that rotates at ~0.1 Hz (Pollard et al., 2007), was synthesized with a fluorene stator. Meanwhile, MM 4 is an analog to MM 1 that lacks a stereogenic center at the allylic methyl site, which confers preference for unidirectional rotation. Hence, MM 4 ³IODSV´^ ELGLUHFWLRQDOO\^ DQG^ VZLWFKHV^ VWRFKDVWLFDOO\^ EHWZHHQ^ photoisomerization states. All four of these motors possess an appended aniline that shifts their absorption into the visible spectrum, enabling their observation by visible-light microscopy and activation of rotation by visible light (Alaya-Orozco et al., 2020). These terminal amines are protonated at physiological pH, promoting their interaction with the hydrophilic heads of lipid bilayers in cell or organelle membranes. FIG.1D shows the calcium responses of cells treated with each MM and light. MM 3 was used at 3x concentration because of its lower extinction coefficient relative to the other MM (FIG.13, Table 1). Fast-rotating MM 1 and MM 2 elicited rapid increases in intracellular calcium. MM 1 elicited high- amplitude transients that peak ~10-20 s after stimulation and then decay over the next minute, whereas MM 2 elicited a more stable increase in intracellular calcium that does not decay as quickly as MM 1. The different calcium release kinetics induced by MM 1 and MM 2 may be related to differences in their photoisomerization efficiency (García-López et al., 2020). Meanwhile, slow-rotating MM 3 elicited no change in calcium activity upon irradiation, even at 3× the concentration and twice the stimulus intensity used to activate MM 1 and MM 2 (FIG.1D). MM 4, the fast-rotating motor with no preference for unidirectional rotation, elicited only small changes in calcium concentration. This experiment provides evidence to link MM rotation speed and directionality to their evoked cell signaling behavior. Table 1. Properties of MM 1-4. Partition coefficients and total polar surface area were calculated using the molInspiration online calculator. milogP represents the logarithm of the partition coefficient between octanol and water, used to represent hydrophobicity (higher values are more hydrophobic). Rotation rates were provided using the thermodynamics of the thermal helix inversion step. MM structures provided for reference. EXAMPLE 2 – Evidence of Calcium Waves Caused by Intracellular MM Actuation Next, the mechanism was studied behind MM-driven calcium signaling. Calcium equilibrium in the cytosol is regulated by both export across the plasma membrane and uptake by the ER via membrane ATPases (FIG. 14A) (Clapham, 2007). Consequentially, the cytosolic concentration of calcium is typically low (~100 nM) compared to those found inside the ER or extracellular medium (~1.5 mM). Cytosolic calcium spikes commonly involve the entry of calcium from one of these two locations. Fluorescence microscopy showed that MM internalize within cells and interact with subcellular organelles, including mitochondria and the ER (FIGS. 14B, 15, and 16). Since MM are distributed primarily within cells, without wishing to be bound by any theory, it is believed that the MM-induced calcium responses are due to the release of calcium from intracellular stores. To test this hypothesis, calcium stores were depleted inside and outside of HEK293 cells and blocked various plasma membrane or ER calcium channels prior to stimulation (Table 2). Table 2. Pharmacological blockers and treatments employed. Cells treated with MM 1 and stimulated by light pulses in the absence of extracellular calcium (FIG. 14C) showed no differences in response amplitude compared to a positive control in calcium- containing medium. Similar results were observed when plasma membrane-bound channels were blocked. Treatment of cells with ruthenium red (RR), a pharmacological inhibitor of temperature- sensitive vanilloid transient receptor potential (TRP) channels (Vrins et al., 2009), did not decrease the magnitude of MM-induced calcium responses (FIG. 14D). Similarly, treatment of cells with Gd ³⁺ , which is commonly used to block the effects of mechanosensitive plasma membrane channels such as Piezo1, Piezo2, and TRPC4 (Hamill & McBride, 1996), did not affect the observed responses (FIG. 14E). In all, the experiments show that plasma membrane-bound TRP channels and extracellular calcium do not appreciably contribute to MM-induced calcium responses. On the other hand, cells treated with MM 1 and thapsigargin, a sarco-endoplasmic reticulum calcium pump (SERCA) antagonist that depletes intracellular calcium (Thastrup et al., 1990) did not show any measurable calcium flux upon light stimulation (FIG. 14F; P = 0.00257 < 0.01). This result implies that MM-evoked calcium responses arise from the release of ER-bound calcium stores by MM 1. Further mechanistic studies were conducted to determine how MM activation releases calcium from the ER. The mammalian ER predominantly expresses two large tetrameric calcium channels: IP ₃ receptors (IP ₃ Rs) and ryanodine receptors (RyRs) (Clapham, 2007; Bock & Ackrill, 2008). In IP ₃ - mediated calcium signaling, G-protein coupled receptors (commonly Gq/11 subtypes) expressed in the SODVPD^PHPEUDQH^DFWLYDWH^SKRVSKROLSDVH^&ȕ^^3/&ȕ^^D QG^W\URVLQH^NLQDVH^UHFHSWRUV^DFWLYDWH^3/&^ to cleave phosphatidylinositol 4,5-biphosphate into diacylglycerol and IP ₃ (Bock & Ackrill, 2008). IP ₃ can then diffuse to the ER, where it binds to IP ₃ R and causes calcium release. This network is generally rHIHUUHG^WR^DV^VLPSO\^³FDOFLXP^UHOHDVH´^GXH^WR^LWV^XELTXLW \^LQ^UHFHSWRU^ELRORJ\^^5\5V^DUH^DOVR^H[SUHVVHG^ in many cell types and amplify existing calcium signals through calcium-induced calcium release. Treatment of cells with ryanodine (Ry; 100 µM) to block RyR signaling has no effect on response amplitude (FIG. 14G) in HEK293 cells. However, treatment of cells with xestospongin C (XeC; 25 µM), a known antagonist of IP ₃ R (Gafni et al., 1997), significantly diminished the strength of cellular responses to MM (FIG. 14H; P = 0.0167 < 0.05). Similar effects were observed when cells were treated with the PLC antagonist U-73122 (U-73; 10 µM) as an alternate method of blocking IP ₃ signaling (FIG. 14I; P = 0.0281 < 0.05). Furthermore, MM-induced responses were also inhibited in cells treated with cytochalasin D (Cyto D; 2 µM), an inhibitor of F-actin polymerization that disrupts PLC signaling by increasing the spatial distance between PLC and IP ₃ R (FIG.14J; P = 0.01762 < 0.05) (Riberio et al., 1997). These results implicate IP ₃ signaling as a primary driver of MM-induced calcium waves. The IP ₃ pathway is known to contribute to mechanosensitive calcium currents (Xu et al., 2018) and is involved in the induction of ICW in response to mechanical stimulation with a micropipette (Tsutsumi et al., 2009; Sanderson et al., 1990). EXAMPLE 3 – Mechanistic Study of MM-Induced ICWs Next, investigations into whether MM-elicited ICW could be used to modulate calcium-driven biological processes, such as the beating activity and contraction of cultured cardiomyocytes. FIG. 17 shows the effects of MM stimulation on primary rat cardiomyocytes. MM distribute to the sarcoplasmic reticulum (SR; FIG. 17A), where subsequent light activation triggers localized calcium release (FIG. 17B). MM-driven calcium release initially leads to localized myocyte contraction at the site of stimulation (FIG. 17C, kymograph 1, top arrow) likely due to the calcium-mediated activation of troponin and subsequent actin-myosin cross-bridge formation (Feher, 2007). Then, SR calcium release induces beating in quiescent cardiomyocytes and accelerated beating in active cardiomyocytes (FIG. 17C, bottom arrow in kymograph 1 and arrow in kymograph 2). The behavior of colonies of cardiomyocytes in contact with cells stimulated with MM and light was tracked to determine whether the MM could be used to drive biological behaviors coordinated in networks of cells, such as contraction. Colonies of cardiomyocytes adjacent to stimulated cells responded to stimulation by firing action potentials (APs) or participating in the generated calcium wave (FIG. 17D, 18, and 19). Activation of adjacent cardiomyocytes in response to stimulation could be prevented by either inhibiting IP3-mediated calcium release in the stimulated cell (FIG. 17E) or by preventing the influx of calcium from outside the cell during AP firing (FIG. 17F). Cells stimulated with MM 1 and light in calcium-containing medium exhibited firing rates of 5.1 spikes min ^-1 cell ^-1 , whereas cells stimulated with MM 1 and light in the presence of PLC inhibitor (U-73; 10 µM) exhibited firing rates of ~0.8 spikes min ^-1 cell ^-1 (P < 0.0001 by a one-tailed Welch’s t-test). Meanwhile, cells stimulated in the absence of extracellular calcium did not exhibit any spiking activity, suggesting that the increased activity of cardiomyocyte colonies in response to MM may be due to the action of voltage- gated ion channels in the plasma membrane of myocytes. These ion channels are likely triggered by local depolarization of the membrane induced by SR calcium release (Stuyvers et al., 2000). These experiments show that biological behaviors coordinated in networks of cells, such as contraction, can be controlled by intracellular MM-induced calcium wave generation. EXAMPLE 4 – MM Induce Muscle Contraction In Vivo Finally, using an in vivo model of muscle contraction, it was investigate whether MM-induced ICW can control biological activity at the organism level. For this purpose, Hydra vulgaris was chosen as a model system for muscle contraction. Hydra are radially symmetric, millimeter-sized freshwater cnidarians containing tentacles, an oral region, and an aboral region connected by a long, tubular body column. In the oral region, Hydra have a dome-VKDSHG^VWUXFWXUH^FDOOHG^D^³K\SRVWRPH´^VXUURXQGHG^E\^D ULQJ^RI^WHQWDFOHV^^$W^WKH^RWKHU^H[WUHPLW\^^WKH\^KDYH^D^IRRW^ FDOOHG^WKH^³SHGXQFOH^´^ZKLFK^WKH^DQLPDO^XVHV^ to attach to substrates (FIG. 20A). Hydra were chosen as a model system because of their small size, lack of chitin layer, excitable epitheliomuscular tissue, and simple nervous system. In addition, Hydra exhibit spontaneous and stimulus-controlled contractions, both driven by ICW (Wang et al., 2020), which can be directly visualized due to their transparent body (Berridge, 2012). In the experiments, Hydra lines genetically engineered to express the calcium indicator GCaMP7b in their endothelial epitheliomuscular tissue were used (see Example 6). Prior to stimulation experiments, Hydra were loaded with MM by incubating with solutions containing 24 µM of MM for 24 h (FIG.20B). Distinct stimulation protocols were employed to cause either local ICW or whole-body contraction (FIG. 20C). First, treatment of MM-loaded Hydra with pulses of laser light administered to a small region of the body column (Protocol I) caused ICW emanating from the site of stimulation (FIGS.20D and 21). Similar to ICW evoked in vitro, these ICW propagated throughout the Hydra body column according to the degree of electrical connectivity of the stimulated cells. Distinct propagation kinetics were observed when stimulating different regions of Hydra simultaneously. Second, MM activation was used to attempt to drive whole-body Hydra contractions by administering laser stimuli to the oral region (Protocol II). The oral region were targeted because mechanical stimulation of this region has been shown to stimulate burst contraction, likely via the sensory neurons that cluster in this region (Kinnamon & Westfall, 1981; Kinnamon & Westfall, 1982; Dupre & Yuste, 2017). When laser stimuli were delivered to the oral region of Hydra treated with fast-rotating MM 1 and 2 (Protocol II), they exhibited contraction bursts associated with whole-body calcium waves similar to those observed with macro-mechanical stimulation (Badhiwala et al., 2020). Fast-rotating MM were generally more successful in eliciting both regional ICW (Protocol I) and whole-body contractions (Protocol II). FIGS. 20E-20I show responses from MM-treated Hydra when stimulated via Protocol I to elicit regional ICW. Furthermore, FIG. 20J compares the response rates of Hydra treated with each MM for exhibiting regional ICW. Fast-rotating MM, including MM 1, MM 2, and even non-unidirectional fast motor MM 4, consistently elicited robust regional ICW upon stimulation of the body column (Protocol I). Occasional responses were also observed from Hydra treated with slow-rotating MM 3, but the response rate of these Hydra was not significantly different from solvent-only controls (FIG. 20J). Hydra also demonstrated marked differences in response kinetics depending on the type of MM employed. Fast, unidirectionally rotating MM elicited appreciably quicker responses (12.76 s for MM 1 and 9.05 s for MM 2) than slow or non- unidirectionally rotating MM (15.46 s for MM 3 and 16.6 s for MM 4; FIG.20K). Similar trends were observed for whole-body contractile response rates across Hydra treated with different MM and light conditions (see Example 6 for a detailed description of the response rate calculation). FIG. 20L & 20M show a representative whole-body contraction and GCaMP7b fluorescence trace from a typical experiment using MM 2 and stimulation using Protocol II. In these experiments, the fastest-rotating MM, MM 2, was most successful at inducing Hydra contraction, demonstrating a response rate of 86% (FIG.20N). This fast-rotating MM elicited contraction of Hydra at a higher rate than light alone (P < 0.00001) or slower-rotating MM 3 (P < 0.00001) by Fisher’s Exact Test. MM 1 also elicited contraction at a significantly higher rate than light alone (P = 0.0199 < 0.05), while the slow-rotating MM 3 (P = 0.5325 > 0.05) did not elicit contraction at a significantly higher rate than light alone. Interestingly, MM 4, which rotates quickly but non-unidirectionally, elicited Hydra contraction with a response rate of 65% and was significantly (P = 0.0439 < 0.05) more effective than light alone. MM 4 also elicited regional ICW in Hydra despite causing only weak responses in vitro. These results imply that even the smaller responses elicited by MM 4 in vitro can be amplified in vivo across networks of cells. Consequentially, rotor speed is a better indicator of the ability of MM to drive Hydra contraction than rotor unidirectionality. Further experiments are needed to elucidate both the biological machinery responsible for amplifying MM-induced signals and the factors influencing MM propensity for causing ICW in Hydra. The contractile behavior of Hydra in relation to the presentation of stimulus is detailed in FIGS. 22-26. Hydra appeared to exhibit a photic response to light in the absence of MM (FIG.26; P = 0.0525 > 0.05) consistent with the photosensitivity of the hypostome and tentacles described previously (Guertin & Kass-Simon, 2015). However, fast-rotating MM actuation was notably superior at driving muscle contraction compared to light alone. Peak identification algorithms were employed to track calcium spikes in the fluorescence data and contraction bursts across the timescale of the experiments. In Hydra treated with MM 2 and light, contraction onset occurs predominantly upon the presentation of the stimulus, and a high density of contraction bursts appears 5-10 seconds later (FIG. 23). In the absence of MM, this relationship weakens dramatically. In the absence of light, it disappears completely (FIG. 26). These results suggest that the actuation of fast-rotating MM can control the behaviors exhibited by Hydra over the time scale of the experiments. Table 3. Hydra dataset characteristics. EXAMPLE 5 – MM Induce Action Potentials and Beating in Cardiomyocytes MM-elicited ICW can be used to modulate calcium-driven biological processes, such as the beating activity and contraction of cultured cardiomyocytes. FIG. 5 shows the effects of MM stimulation on primary rat cardiomyocytes. MM distribute to the sarcoplasmic reticulum (SR; FIG. 5A), where subsequent light activation triggers localized calcium release (FIG. 5B). MM-driven calcium release initially leads to localized myocyte contraction at the site of stimulation (FIG. 5C, kymograph 1, top arrow) likely due to the calcium-mediated activation of troponin and subsequent actin-myosin cross-bridge formation. Then, SR calcium release induces beating in quiescent cardiomyocytes and accelerated beating in active cardiomyocytes (FIG. 5C, bottom arrow in kymograph 1 and arrow in kymograph 2). The behavior of colonies of cardiomyocytes in contact with cells stimulated with MM and light was tracked to determine whether MM could be used to drive biological behaviors coordinated in networks of cells, such as contraction. Colonies of cardiomyocytes adjacent to stimulated cells responded to stimulation by firing action potentials (APs) or participating in the generated calcium wave (FIG. 5D). Activation of adjacent cardiomyocytes in response to stimulation could be prevented by either inhibiting IP3-mediated calcium release in the stimulated cell (FIG. 5E) or by preventing the influx of calcium from outside the cell during AP firing (FIG. 5F). Cells stimulated with MM 1 and light in calcium-containing medium exhibited firing rates of 5.1 spikes min ^-1 cell ^-1 , whereas cells stimulated with MM 1 and light in the presence of an inhibitor of IP ₃ signaling (U-73; 10 µM) exhibited firing rates of ~0.8 spikes min ^-1 cell ^-1 (P < 0.0001 by a one-tailed Welch’s t-test). Meanwhile, cells stimulated in the absence of extracellular calcium did not exhibit any spiking activity, suggesting that the increased activity of cardiomyocyte colonies in response to MM may be due to the action of voltage- gated ion channels in the plasma membrane of myocytes. These ion channels are likely triggered by local depolarization of the membrane induced by SR calcium release. These experiments show that biological behaviors coordinated in networks of cells, such as contraction, can be controlled by intracellular MM-induced calcium wave generation. EXAMPLE 6 – Molecular Motors Induce Calcium Release in C2C12 Myoblasts MM rotation occurs unidirectionally through a series of photoisomerization and thermal helix inversion steps between two main components: the rotor and the stator (Roke et al.,2018) (FIG.36A & B). Upon excitation with 405-nm light, the alkene connecting the rotor and stator undergoes a cis-trans photoisomerization (<180° rotation) that yields the metastable isomer. To complete the first half- rotation (180° rotation), the metastable isomer goes through a thermal helix inversion where it can overcome the energy barrier imposed by steric hindrance with the stator. The MM can then be excited with another photon to repeat the photoisomerization and thermal helix inversion steps and complete a full 360° rotation. An important property of MM rotation is its unidirectionality. Unidirectional rotation distinguishes MM rotation from random molecular rotations along single bonds that can occur in any molecule. Directionality in molecular rotation enables MMs to exert greater work on their surroundings, which can be used to initiate and control biological activity. Both the unidirectionality and speed of rotation have been shown to be important factors for controlling biological activity with MMs and establishing MM activation as having a mechanical mechanism of action (Beckham et al.,2023; Santos et al.,2022; Santos et al.,2023; García-López et al.,2017). C2C12 myoblasts treated with fast (3 MHz)21 and unidirectionally rotating MM 1 and Fluo- 4 exhibited robust intracellular calcium release when stimulated with 405-nm light for 500 ms (FIGS.28 & 36C-D). Fluo-4 is an intracellular calcium dye that fluoresces green when binding to calcium and is commonly used to observe intracellular calcium spikes in many cell types. Control cells treated with only DMSO did not exhibit calcium release, confirming that MM 1 was the driver of the observed effect, not any thermal effects from the laser stimulation. Localization images indicate that both MM 1 and Fluo-4 permeate through the cell membrane after 45 minutes of incubation (FIG.29). C2C12 cells treated at lower laser powers exhibited lower calcium release, and those treated for 1 s instead of 500 ms exhibited larger calcium release (FIG.30). EXAMPLE 7 – Calcium Release is Caused by Fast Unidirectional Molecular Motion Two control motors were utilized to show that fast unidirectional molecular motion is the primary cause of calcium release in C2C12 myoblasts. MM 2 (~3 MHz) (Beckham et al.,2023) is a fast bidirectional motor with an identical structure to MM 1 except it is missing the methyl substituent at the allylic position of the rotor. The methyl substituent creates unidirectionality in molecular rotation by creating a lower energy barrier to thermal helix inversion when the molecule rotates in one direction versus the other. Without the methyl, MM 2 has equal energy barriers when rotating in either direction, which favors one direction over the other, eliminating unidirectionality in its rotation. MM 3 was used as a slow motor, with a rotation rate of 0.1 Hz (Pollard et al.,2007). The magnitude of calcium release caused by MM 1 (fast, unidirectional) was compared to that caused by MM 2 (fast, bidirectional) and MM 3 (slow, unidirectional). MM 1 produced calcium transients several times larger in magnitude than MM 2, while MM 3 did not induce any calcium release (FIG. 37C). The use of these control motors creates a correlation between fast unidirectional rotation and the elicited cellular calcium responses, providing convincing evidence that the calcium release is a mechanically driven effect rather than thermal or photodynamic. Additionally, to further confirm that the cellular calcium release is not the result of a photodynamic effect caused by reactive oxygen species (ROS) generation, ROS generation was measured from each MM using the ROS sensitive dye CellROX green. CellROX fluoresces when oxidized by ROS in living cells and can be used to measure general oxidative stress in cells due to ROS generation. Cells treated with MM 1 and light generated more ROS than the DMSO negative control but less ROS than positive controls using UV light irradiation for 1 min and incubation in H ₂ O ₂ for 1 hr (FIG.31). To confirm that the ROS generated by MM 1 was not causing intracellular calcium release, cells were treated with a combination of thiourea (TU, 50 mM) and sodium azide (SA, 1.25 mM) to scavenge the ROS that were produced. Treatment with both 1x and 0.2x concentrations of scavengers showed a decrease in ROS generation by MM 1 without changing the magnitude of calcium release (FIG. 37C). If ROS generation by MM 1 was the cause of calcium release, then less calcium release would be expected with treatment of ROS scavengers. The fact that calcium release remains unchanged despite the decrease in ROS further suggests that photodynamic effects are not the cause of the induced calcium release in C2C12 myoblasts. The UV-Vis spectrum of each motor was also acquired in DMSO (FIG.37D) to ensure that the difference in absorbance at 400 nm was not the cause of larger or smaller responses. MM 1 and MM 2 have nearly identical absorbances at 400 nm, while MM 3 has a much smaller absorbance. To ensure that this lower absorbance is not the reason for MM 3 having lower calcium release, calcium release was also measured with MM 3 at 3 times higher concentration (FIG. 32) and no measurable increase in calcium release was observed at this higher concentration. EXAMPLE 7 – MM-Driven Calcium Release in C2C12 Myoblasts Occurs Through the IP3 Pathway Previous work performed by Beckham et al. (Beckham et al.,2023) showed that MMs induced cellular calcium release from the endoplasmic reticulum in HEK293 cells by activating the IP3 pathway. Here it is shown that the IP3 pathway is the primary cellular signaling pathway that generates calcium responses in C2C12 myoblasts. The effects of MM stimulation on other common pathways related to calcium signaling were also measured, including the cAMP pathway and receptor tyrosine kinases (RTKs). The IP3 pathway (Molgó et al.,2004; Decrock et al.,2013) is initiated with G protein coupled receptors (GPCRs) in the cell membrane. Under normal IP3 pathway activation, a ligand will bind to specific GPCRs that then activate their associated G protein, Gჴq/11. The G proteins then activate phospholipase C (PLC) (Bill and Vines; 2020), which cleaves PIP2 into diacylglycerol and IP3. After this, IP3 diffuses across the cytosol and binds to IP3 receptors (IP3R) in the ER membrane, which open up to release high concentrations of calcium into the cytosol. It was determined that MMs activate the IP3 pathway by inhibiting key proteins along the pathway. If inhibition of a specific protein decreases the magnitude of the observed calcium responses, then it can be assumed that the targeted protein played an important role in propagating the calcium signaling pathway that was initiated by MMs. When PLC is inhibited using 10 µM U-73122, the observed calcium responses are completely abolished (FIG. 38A). Further upstream, both subunits of the G proteins specific to the IP ₃ pathway were inhibited XVLQJ^^^^^^0^JDOOHLQ^WR^LQKLELW^*ȕȖ^DQG^^^^0^ )5^^^^^^^WR^ LQKLELW^*Į^^^^ ,QKLELWLRQ^RI^HDFK^RI^ WKHVH^SURWHLQV^UHVXOWHG^ LQ^D^a^^^^UHGXFWLRQ^ LQ^ WKH^ observed calcium response (FIGS. 38A & B). When both gallein and FR900359 are used simultaneously, a similar decrease of ~50% also occurs (FIG.33). The difference in calcium responses between PLC inhibition and GPCR inhibition indicates that MMs may be partially activating PLC through other means, in addition to GPCR- mediated IP ₃ signaling. This may occur either through direct MM activation or indirectly through MM activation of a different signaling pathway. It is known that RTKs can also activate PLC (Bill and Vines, 2020). When RTKs were inhibited using 1 µM nintedanib no decrease in magnitude of the elicited calcium responses was observed (FIG.38F). These results show that MMs initiate IP ₃ signaling in C2C12 myoblasts by directly activating GPCRs, the furthest upstream protein in the IP ₃ pathway. It is known that GPCRs are mechanosensitive to various stimuli in the form of stretch or shear stress (Marullo et al.,2020). Furthermore, intercellular IP3-mediated calcium signaling is known to occur by means of mechanical stimulation, often induced by mechanical stimulation with a micropipette (Tsutsumi et al.,2009; Leybaert and Sanderson, 2012; Sanderson et al.,1990). Therefore, it is hypothesized that MMs activate GPCRs through molecular mechanical forces that result from fast unidirectional rotation. The cAMP pathway is another pathway initiated by GPCRs that may influence calcium signaling. It is also known to cause phenomena observed in the paper by Beckham et al. (Beckham et al.,2023), such as cardiac myocyte contraction, although cAMP signaling was not measured in that study. Like the IP ₃ pathway, the cAMP pathway is initiated by GPCR activation. GPCRs activate their associated Gs protein, which then activates adenylyl cyclase. Adenylyl cyclase synthesizes cAMP from ATP, and cAMP then diffuses to the cytosol to activate protein kinase A (PKA), which can trigger a series of different cellular pathways and other downstream effects. Some of these effects may influence calcium signaling in a variety of ways (Reiken et al.,2003; Gehlert et al.,2015; Kuo and Ehrlich, 2015; Emrick et al.,2010). The effect of cAMP pathway inhibition on the elicited calcium signaling responses was measured by using 100 µM SQ22536 to inhibit adenylyl cyclase (FIG.38D) and 200 µM cAMPS-Rp (FIG. 38E), a cAMP antagonist that inhibits protein kinase A (PKA) activation. The result of these treatments was a small reduction in calcium signaling. At this moment it cannot be concluded whether this effect is because MMs also activate the GPCRs associated with the cAMP pathway, or if inhibition of adenylyl cyclase and PKA naturally affects normal calcium signaling pathways, regardless of MM stimulation. EXAMPLE 8 – Cells Lose Responsiveness to MM Stimulation During Differentiation C2C12 cells will undergo differentiation from myoblasts to multinucleated myotubes when allowed to grow to confluence. This process occurs over the course of several days and can be sped up by replacing normal growth media with low serum differentiation media (Jang et al.,2022). The responsiveness of C2C12 cells to MM stimulation changes was tracked as they went through the process of growth and differentiation (FIG. 39). When plated on the first day, the cells are in low confluency, and show clear morphology of myoblasts. The cells reach around 100% confluency on day 4 (FIG. 39A), at which point they begin to differentiate to form the myotubes. They show lowest uptake of Fluo-4 and nearly no responses. After about 9 days of growth in regular growth media, myotubes begin to form, which have a fibrous, striated and multinucleated appearance, and the uptake of Fluo-4 could be observed again. The cells’ responsiveness to MM stimulation changes throughout the differentiation process (FIG.39B). During the initial three days, the C2C12 myoblasts respond to MM 1 stimulation, resulting in the release of intracellular calcium, although with a slight decrease of the responsivity from day 1 to day 3. From day 4 to day 8, during which they are differentiating into myotubes, the cells lose their responsiveness to MM stimulation. However, once the myotubes begin to form on day 9, they display an increase in Fluo-4 uptake as well as an increase in responsiveness to MM stimulation. There are several possible explanations for this decrease in activity, all of which it is proposed are due to the down-regulation of various proteins during the differentiation process. After differentiation is complete, these proteins are upregulated again, which would explain the recovery in responsiveness in fully differentiated myotubes. The first explanation is that C2C12 myoblasts down- regulate the needed enzymes to cleave the ester group off of Fluo-4, which is necessary for it to bind to calcium and fluoresce. Literature reports using RNA sequencing have shown that esterases are down- regulated during C2C12 differentiation (Kislinger et al.,2005; Azar et al.,2021; He et al.,2017; Lyu and Jiang, 2022). In this case, it is likely that MMs are still capable of inducing calcium release in differentiating myoblasts, but the cells would not uptake and cleave enough Fluo-4 to be able to visualize it. The second explanation is that changes in calcium responsivity occur because of changes in the expression of calcium-signaling proteins, such as Gჴq/11 or PLC. This would explain why the cells stop releasing calcium during differentiation, but fails to explain the decrease in baseline Fluo-4 expression. Given these results, it is hypothesized that the down-regulation of esterases is the most likely reason for the observed effects. EXAMPLE 9 – MM 1 induces skeletal myotube contraction by releasing intracellular calcium After differentiation is complete, C2C12 myotubes have the ability to contract in response to an influx of intracellular calcium (Kaji et al.,2010; Dennis et al.,2001). The skeletal muscle cell contraction takes place because of the binding of the myosin and actin. Under normal circumstances, the binding sites on the actin are blocked by tropomyosin, preventing their binding to the head of myosin (FIG. 40A). When the intracellular calcium level increases, calcium ions will bind to the troponin subunits, which then draw the tropomyosin aside to expose the binding sites on actin. This enables actin to bind with myosin, resulting in the skeletal muscle cells contraction. Given the mechanism and the results that the MM 1 could induce intracellular calcium release, it is hypothesized that MMs could induce C2C12 myotube contraction by means of an intracellular calcium wave. MM 1 induced localized calcium responses in C2C12 myotubes after stimulation with light for 1.5 s (FIG. 40B), which resulted in strong myotube contraction (FIG. 40C). To quantitatively demonstrate cellular contraction, the image subtraction method was used (FIG. 35). This method yielded images where the pixel intensity corresponds to movement over the course of the experiment (FIG.40C), allowing us to easily visualize and quantify contraction. Analysis of stimulated cells with this method showed that MM 1 induced strong contraction in C2C12 myotubes (FIG. 40D). Strong cellular contraction did not occur when cells were treated with DMSO, MM 2, or MM 3, suggesting that contraction was caused by the large calcium transients from MM 1 stimulation. To further show that contraction was a result of the induced calcium release, myotubes were treated with U73. These cells showed contraction magnitude equal to that of the DMSO control. These results align with the hypothesis that MMs are capable of inducing skeletal muscle contraction by inducing strong intracellular calcium waves. MMs provide a light-based spatiotemporal method of mechanically triggering skeletal muscle contraction. It was demonstrated that MMs mechanically induce calcium release and muscle contraction in C2C12 cells through fast unidirectional rotation when stimulated with 400-nm light. The unidirectionality and rotation rate as the primary causes of calcium release were also isolated, which highlights the use of MMs as a mechanical form of stimulation. This research offers an alternative approach to the traditional methods of inducing muscle contraction, such as the use of drug targets or electrical stimulation (Kaji et al.,2010) and it offers the advantages of precise control over the location, duration, and magnitude of stimulation. The use of MMs for inducing muscle contraction has potential as a treatment of muscle-related diseases. This work demonstrates how intracellular molecular mechanical forces can be used to control cellular signaling and macroscopic biological activity. EXAMPLE 10 – Experimental Methods Synthetic Chemistry: Synthesis and characterization information on the MM is provided elsewhere (Alaya-Orozco, C. et al.) MM were dissolved in DMSO at a concentration of 8 mM and sonicated for a few seconds prior to use. MM solutions were stored at -20 ºC in aluminum foil-wrapped containers to avoid degradation. Cell Culture and Preparation of Cells for Microscopy: HEK293 cells were chosen as the principal model system due to their prevalence in electrophysiological interrogation. HEK cells, as with most excitable or non-excitable cells, are known to exhibit calcium responses (Sinnecker & Schaefer). HEK293 cells, HeLa cells, and N2A cells were cultured in DMEM (10% FBS, 1% penicillin/streptomycin) and passaged at < 90% confluence. To grow cardiomyocytes, a dissColved rat heart (TransnetYX ^© ) was triturated, centrifuged, and resuspended in cardiomyocyte growth medium (TransnetYX ^© catalog #SKU-NBCG) and seeded at a concentration of 60,000 cells cm ^-2 . Growth substrates were pre-treated with 1% gelatin solution for 3 h, then washed with PBS. Cardiomyocytes were allowed to grow for 4 days, after which the growth medium was exchanged for cardiomyocyte maintenance medium (TransnetYX ^© catalog #SKU-NBCM). Experiments were conducted from day 4 to day 6. Imaging was conducted in imaging extracellular buffer (iECB; 119 mM NaCl, 5 mM KCl, 10 mM HEPES, 2 mM CaCl2, 1 mM MgCl2 (pH 7.2); 320 mOsm). Imaging in calcium-free medium was conducted in phosphate-buffered saline. Cells were prepared for imaging by seeding a 35 mm Ibidi imaging dish with ~50,000 cells in 1 mL of DMEM, and grown at 37 ºC, 5% CO ₂ for 2 days. Prior to imaging, cells were incubated with dyes and/or molecules resuspended in complete growth medium at the appropriate concentration (MM 1 (8 µM), MM 2 (8 µM), MM 3 (24 µM), MM 4 (8 µM), Fluo-4 (2 µM)). MM and Fluo-4 were loaded into cells for 45 min. Cells treated with thapsigargin were exposed for 30 min after MM and Fluo-4 loading. Cells treated with organelle-targeting dyes were exposed for 5 min after MM loading. Ruthenium red and Gd ³⁺ were included in the imaging medium during stimulation and were associated with cells for 10 min prior to imaging. At the end of incubation, this medium was replaced with the iECB. Unless otherwise specified, all experiments were replicated in triplicate. In Vitro Imaging and Stimulation: Cells were loaded in a Nikon A1-Rsi confocal system mounted on a widefield Ti-E fluorescence microscope. Imaging was conducted using a 60x water immersion objective (NA of 1.27, 0.17 mm working distance). Green fluorophores (Fluo-4, MitoTracker Green) were excited using a 488 nm photodiode laser. Red fluorophores (ER-Tracker-Red, PI) were excited using a 561 nm photodiode laser. Deep red fluorophores (cellMask plasma membrane stain) were excited using a 630 nm photodiode laser. Laser stimulation for in vitro experiments was performed with a 400 nm photodiode laser (Coherent OBIS ^TM LX SF) operating in a fluorescence- recovery-after-photobleaching (FRAP) experiment mode, delivering up to 6.4×10 ² W cm ^-2 at sample level. Unless otherwise specified, all experiments were conducted using a stimulus irradiance of 3.2×10 ² W cm ^-2 . Cardiomyocyte experiments were conducted using a stimulus irradiance of 5.1×10 ² W cm ^-2 . Power was calibrated using a Thor Labs S130C laser power meter. Stimulation was targeted to a circular area of diameter 5 µm in a 250 ms pulse, during which the laser rasters across the entire region of interest. An additional laser stimulation set-up was used to verify the requisite stimulation power and demonstrate excitation in a non-scanning laser mode (FIG.27). Fluo-4 fluorescence was collected for 30 s before and 2 min after stimulation. Images were collected using a Galvano scanner operating at 0.94 fps. In selected experiments, images were also collected using a resonant scanner operating at 7.7 fps. Colocalization Analysis: Cells were treated with MitoTracker Green (ThermoFisher, 400 nM), ER Tracker Red (ThermoFisher, 500 nM), and cellMask Deep Red Plasma Membrane Stain (ThermoFisher, 500 nM). ER Tracker Red and MitoTracker Green were loaded into cells for 45 min in complete growth medium. Then, cellMask Deep Red Plasma Membrane Stain was loaded into cells for 5 min and cells were subsequently loaded into the microscope chamber. Images for co-localization analysis were collected in a Nikon A1 confocal microscope using a 60x water immersion objective. Z- stack images of distance 0.5 µm spanning a minimum 20 µm range were collected and processed using the Coloc-2 plugin in Fiji. Colocalized pixel intensity maps were generated using the colocalization threshold function in Fiji. Pharmacological Experiments: In pharmacological blocking experiments, cells were loaded with MM and Fluo-4 as previously described. Typical imaging experiments in previously described extracellular buffer were then conducted as a positive control. Then, the imaging buffer was replaced, and the cells were treated as required for each experiment. After a brief recovery period, the cells were imaged again, and six different cells were stimulated. Experiments in calcium-free imaging buffer used phosphate buffered saline. Thapsigargin (Th; 1 µM) and Cytochalasin D (Cyto D; 2 µM) were incubated with cells in complete growth medium for 1 h (Th) or 2 h (Cyto D) before imaging. Ruthenium red (RR; 1 µM), gadolinium (Gd; 50 µM), ryanodine (Ry; 100 µM), xestospongin C (XeC; 20 µM), and U-73122 (U-73; 10 µM) were administered directly into the imaging medium. Cells were incubated in the medium for ~5 min prior to imaging. Traces presented are representative results across at least six cells from single experiments, while bar graphs represent the average results across at least three distinct experiments. Hydra Preparation, Stimulation, and Imaging: Hydra were raised in Hydra medium containing CaCl ₂ ڄ2H ₂ O, MgCl ₂ ڄ6H ₂ O, KNO ₃ , NaHCO ₃ , and MgSO ₄ in deionized water at 18 ºC in a light-cycled (12 h light, 12 h dark) incubator. Hydra were fed with an excess of freshly brined Artemia Nauplii (Brine Shrimp Direct, Ogden, UT, # BSEP8Z) three times a week. All experiments were performed at room temperature after starving the animals for 2 days. The transgenic line expressing GCaMP6s under the Actin promoter in neurons was generated by embryonic microinjection by the Yuste lab at Columbia University (Addgene: plasmid #102558). The transgenic line expressing *&D03^E^ XQGHU^ WKH^ (I^Į^ SURPRWHU^ LQ^ HQGRGHUPDO^ HSLWKHOLRPXVFXODU^ WLVVXH^ ZDV^ JHQHUDWHG^ E\^ embryonic microinjection in a collaboration by the Robinson lab (Rice University) and the Juliano Lab (University of California, Davis). Hydra were incubated with chosen MM 24 h before imaging. Hydra treated with MM exhibited noticeable tentacle shortening and reduced spontaneous contraction compared to vehicle-treated Hydra, but no significant toxicity was observed at the concentration of MM employed (24 µM). Stimuli were applied to the oral region using an ROI-driven fluorescence-recovery-after-photobleaching (FRAP) mode in a Nikon A1 confocal microscope. To elicit regional ICW, stimulation was delivered using a 405 nm photodiode laser at 9.0×10 ² W cm ^-2 in 1 s pulses delivered to a 10 µm diameter region-of- interest in the body column of the Hydra. To elicit contraction, stimulation was delivered using a 405 nm photodiode laser at 9.0×10 ² W cm ^-2 in 2 s pulses delivered to the oral region of the Hydra (typical area of ~1,000-2,000 µm ² ). Note that despite the higher stimulation power (1.5x larger) and longer stimulation time (8x longer) used in the Hydra contraction experiments, the Hydra still experiences less incident light per unit area compared to in vitro experiments due to the size of the stimulation region (~50-100x larger depending on the size of the animal). GCaMP6s and GCaMP7b fluorescence were recorded using a 456 nm photodiode laser for fluorophore excitation. Stimuli were presented at irregular intervals at least 60 s apart to prevent interference from periodic spontaneous contractions. Both MM administration and subsequent stimulation treatments were not toxic to the Hydra. Data Analysis – In Vitro: Data were analyzed using custom-written Python scripts. Fluorescence traces of calcium indicator Fluo-4 from cells were imported and processed via the Pandas library. F ₀ was calculated as the average fluorescent intensity in the first 10 frames (~10 s) of acquisition and used to calculate ^F/^ _^ across the length of the recording. Spiking behavior of cardiac myocytes was calculated using the SciPy peak finder function. Data Analysis – Hydra: Fluorescence traces of calcium indicator GCaMP6s in Hydra vulgaris ^{were processed similarly to in vitro data and baseline-corrected to set the minimum measured} _{^F/^^YDOXH^DV^³^´^GXH^WR^WKH^VSRQWDQHRXV^^SHULRGLF^DF WLYLW\^RI^WKH^Hydra. To identify individual calcium} spikes in a contraction burst, the SciPy peak finder function was employed. To identify contraction onset, a simple limit-of-detection peak finding algorithm was used with a threshold value of 1.5. The LQGXFWLRQ^RI^D^FRQWUDFWLOH^³UHVSRQVH´^FRPSULVLQJ^D^FKDQJH^ LQ^ERG\^*&D03^E^IOXRUHVFHQFH^RI^D^IDFWRU^ of 1.5x within 3 s of stimulus presentation was counWHG^DV^D^³VXFFHVV´^LQ^WKH^FDOFXODWLRQ^RI^WKH^UHVSRQVH^ rate. Response rates were calculated across at least 50 presentations of stimuli. Stimuli presented during a time which Hydra are already contracting (^F/^ _^ > 0.3) were discarded. Hydra exhibiting mouth- opening behavior during the experiment were discarded. Effects of spontaneous and photic responses were accounted for by comparison to DMSO and DMSO + light controls. Statistical significance tests were performed using Fisher’s Exact Test. Statistical Analysis: One-tailed Welch’s t-tests were performed to assess differences in cellular responses after pharmacological manipulations, or when treated with MM of different rotation speeds. Fisher’s Exact Tests was used to assess differences in contractile response rates between Hydra vulgaris treated with MM of variable rotation speed and light. * p-value < 0.05, ** p-value < 0.01, *** p-value < 0.001, **** p-value < 0.0001. Excitation in a Non-Scanning Laser Stimulation Mode: In typical experiments, the exciting laser for stimulation was rastered across a defined region-of-interest approximated as a circle of 5 µm diameter. A second stimulation set-up was employed on an epifluorescence microscope to verify that laser rastering is not necessary for excitation. Experiments with a non-rastering laser beam required similar stimulation powers to elicit responses from MM-treated cells (~10 ² W cm ^-2 ). The optical setup were adapted from a single cell fluorescence sensing optical system (Zhao et al., 2021) to deliver a non-scanning laser beam (Coherent Chameleon Discovery) to the specimen from the top, at the excitation wavelength of the MM. The fluorescence signal is collected by an inverted fluorescence microscope from the bottom of the specimen, while an electronic shutter is used to release optical pulses for MM triggering at the desired frequency during fluorescence recording. Assessment of Stimulation Toxicity: The purpose was to use MM to interact with cell signaling. However, several previous studies by the group have explored the same or similar molecules for inducing cell permeabilization and death (Santos et al., 2022; Alaya-Orozco et al., 2020; Gunasekera et al., 2020). These studies used minutes-long light doses rather than the millisecond-scale doses employed in this work. Nevertheless, assessing the effects of MM stimulation on cell viability remains imperative. Potentially toxic effects of MM stimulation on cells were assessed in several ways. The results of these experiments are reported in FIGS. 8-10. First, qualitative analysis of stimulated cells can be used to assess toxicity. For these experiments, HEK293 cells were treated with MM 1 and prepared as was typical for stimulation experiments. At very high stimulation powers, cells exhibited membrane blebbing and runaway calcium accumulation (see FIG. 10A). By reducing the light power, a more suitable light dose was able to find that elicited strong calcium responses from cells without observable toxicity (FIG.10B). Second, once a suitable window of stimulation power had been identified, the effects of stimulation on cells were compared to healthy cells and several positive controls representing mechanisms of cell death. For these experiments, cells were loaded with Fluo-4, CellMask cell membrane labeling dye, and MM 1 and were imaged in the presence of cell-impermeant viability dye propidium iodide (PI; 1 µg mL ^-1 ). The results of these experiments are shown in FIG. 9. The onset of apoptotic cell death in imaged colonies was confirmed by the observation of pyknosis (cell shrinkage) (Hajnoczky et al., 2003), the uptake of small amounts of PI, and the enhanced fluorescence of Fluo-4 in the colony (FIG. 8A). Necrotic cell death was observed by activating MM 1 in situ using a SOLA LED fed through a DAPI excitation filter (395/25 nm, , 166 mW cm ^í2 ) for 5 min (FIG. 8B). Similar conditions have been shown to induce necrotic cell death previously (Tada & Concha, 2001) Using this protocol, cells do not shrink in the 5 min of stimulation, but they uptake large amounts of PI. Such changes were not observed in healthy, unperturbed cells (FIG. 8C) or cells exhibiting MM-driven calcium responses driven by typical protocols (250 ms pulse to a 5 µm diameter at 3.2×10 ² W cm ^-2 stimulation power; FIG.8D). Finally, to account for potential aftereffects of stimulation, isolated HEK293 colonies were grew in a grid pattern by photolithographically patterning polydimethylsiloxane onto Ibidi imaging dishes. Colonies were seeded with 25,000 cells cm ^-2 . Two days after seeding, cells were treated with MM 1 and Fluo-4 using typical protocols (see Example 6), and 10 selected cells were stimulated in selected colonies. Results from these experiments are shown in FIG.9. After 24 h, these colonies were imaged again in the presence of 1 µg mL ^-1 PI to observe any effects of MM stimulation on growth, cell stress, or viability. The PI uptake of stimulated colonies was indistinguishable from untreated colonies. As a positive control, several colonies were irradiated with UV light (SOLA LED fed through a DAPI excitation filter (395/25 nm, 166 mW cm ^í2 ) for 10 min on Day 3 of growth (MM 1 was not present). UV irradiation caused PI uptake into cells immediately and distinguished the UV-treated cells from cells that exhibited MM-induced ICW. In summary, qualitative assessment of the effects of MM stimulation on cells reveal that stimulation does not incur toxicity either by apoptosis or necrosis so long as the light dose administered is appropriately controlled. Effects of Rotation Speed and Directionality: The propensity for unidirectional MM to rotate and exert mechanical force on their environment depend principally on two factors: the rotation rate and the photoconversion efficiency. Both of these depend on MM structure. The rotation rate is determined by the half-life of the thermal helix inversion, which is driven by the steric interactions governing the passage of the rotor over the stator (Pollard et al., 2007). The photoconversion efficiency, also known as the quantum yield of photoisomerization, or )P, represents the proportion of photons absorbed by the molecule that drive molecular rotation (as opposed to fluorescence or non-radiative decay processes). ) _P is primarily influenced by the electronic structure. MM directionality can also be influenced by structure, as the driving force for unidirectional rotation depends upon the presence of a stereogenic center. The selection of different MM of similar physicochemical character allowed us to probe the effects of altered MM speed or directionality on the signaling behavior elicited. MM 1, which rotates at ~3 MHz, elicited the strongest signaling responses in vitro. ICW elicited by MM 1 peaked ~10-20 s after stimulation and decayed over the next minute. Slow-rotating MM 3 did not elicit any noticeable responses in vitro, whereas bidirectional MM 4 elicited inconsistent and weak responses. These results mirror those previously observed when tracking MM diffusion in solution (García-López et al., 2015) and when tracking their ability to permeabilize phospholipid bilayers (García-López et al., 2017). In these experiments, slow-rotating MM were indistinguishable from solvent-only controls, whereas bidirectional MM were distinguishable from controls but did not exert as pronounced an effect as fast, unidirectional MM. MM 2, which has a reported rotation rate of ~43 MHz, also elicited strong responses in vitro, but did not elicit the same release kinetics, instead causing release of calcium to a stable level without decay until several minutes after stimulation. Given that ICW elicited by MM 1 reached a higher amplitude than those elicited by MM 2, alongside the aforementioned difference in release and recovery kinetics, we conclude that MM 1 imparts a stronger stimulatory effect than MM 2 despite its slower rotation rate. The observed recovery by cells treated with MM 1 but not with MM 2 can be attributed to various mechanisms of cellular recovery, including SERCA activity and RyR closing probability, being enhanced by a larger cytosolic concentration of calcium (Clapham, 2007). If MM 2 does not elicit sufficient calcium release to cause accelerated cellular recovery, ICW elicited by MM 2 would persist at stable levels for a longer timeframe than those elicited by MM 1. Since both these motors rotate in the MHz-regime, we anticipate that this difference in their activity can be attributed to their photoconversion efficiency. If a lower proportion of absorbed photons drive rotation in MM 2 as compared to MM 1, this motor would impart a lower mechanical force than MM 1 despite its faster rotation rate. Indeed, previous studies of overcrowded alkene motor dynamics have shown that motors bearing similar core stator structures to MM 2 suffer from lower quantum yields compared to sulfur- bearing core stators (Cnossen et al., 2014). In Hydra, several different trends are observed as compared to in cells. Most notably, MM 4 is able to drive non-trivial signaling behavior in vivo. MM 2 was also highly effective at driving Hydra contraction, and MM 1 and MM 2 were similar in ability to drive body column ICW. Small responses were observed even to stimulation with MM 3, and the Hydra overall seemed a much more sensitive model system than HEK293 cells or cardiac myocytes. Compared to HEK293 cells, Hydra exhibit frequent spontaneous ICW and possess networks of cells that are excitable and electrically connected (Badhiwala et al., 2020). Hence, a response in one cell is more likely to be both amplified by a voltage- gated channel and propagated through gap junctions to other cells. The effectiveness of MM 4 in Hydra but not in cultured cells illustrates how the smaller signals elicited by MM 4 can be amplified and propagated across cellular networks. Further experiments are necessary to untangle the mechanisms underlying the propagation and amplification of MM-induced signaling in Hydra vulgaris. * * * * * * * * * * * * * All of the methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure. While the methods of this disclsoure have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the disclsoure. More specifically, it will be apparent that certain agents which are both chemically and physiologically related may be substituted for the agents described herein while the same or similar results would be achieved. All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the disclsoure as defined by the appended claims.

VIII. References The following references, to the extent that they provide exemplary procedural or other details supplementary to those set forth herein, are specifically incorporated herein by reference: Alaya-Orozco et al., ACS Appl. Mater. Int., 12:410-417, 2020. Aprahamian, ACS Cent. Sci., 2020, 6 (3), 347–358. Ayala Orozco, ACS Appl. Mater. Interfaces, 2020, 12 (1), 410–417. Azar et al., Physiol. Rep., 2021, 9 (1), e14671. Beckham, Nat.Nanotechnol., 2023, 18 (9), 1051–1059. Bilici et al., Front. Chem.9, 2021. Bill and Vines, Adv. Exp. Med. Biol., 2020, 1131, 215–242. Browne and Feringa, Nat. Nanotechnol., 2006, 1 (1), 25–35. Campbell and Smrcka, Nat. Rev. Drug Discov., 2018, 17 (11), 789–803. Carrasco & Hidalgo, Cell Calc., 40:575–583, 2006. Chen et al., Adv. Sci., 2020, 7 (8). Decrock et al., Biochim. Biophys. Acta BBA - Mol. Cell Res., 2013, 1833 (7), 1772–1786. Dennis et al., Am. J. Physiol.-Cell Physiol., 2001, 280 (2), C288–C295. DiFrancesco et al., Nat. Nanotechn., 15: 296-306, 2020. Eelkema et al., Nature, 2006, 440 (7081), 163–163. Emrick et al., Proc. Natl. Acad. Sci., 2010, 107 (43), 18712–18717. Erbas-Cakmak et al., Chem. Rev., 2015, 115 (18), 10081–10206. Garcia-Lopez et al., Nature, 548(7669):567-572, 2017. García-López, Nature, 2017, 548 (7669), 567–572. Gehlert et al., Int. J. Mol. Sci., 2015, 16 (1), 1066–1095. Guinart et al., Proc. Natl. Acad. Sci., 2023, 120 (27), e2301279120. He et al., Sci. Rep., 2017, 7 (1), 15308. Jang et al., Sci. Rep., 2022, 12 (1), 827. Kaji et al., Biomaterials, 2010, 31 (27), 6981–6986. Kislinger et al., Mol. Cell. Proteomics, 2005, 4 (7), 887–901. Klok et al., J. Am. Chem. Soc., 2008, 130 (32), 10484–10485. Kuo and Ehrlich, Cold Spring Harb. Perspect. Biol., 2015, 7 (2), a006023. Lange et al., Pharmaceutics, 13, 2021. Leybaert & Sanderson, Phys. Rev., 92:1359–1392, 2012. Leybaert et al., Physiol. Rev., 2012, 92 (3), 1359–1392. Li et al., Bioact. Mater.6:794–809, 2021. Lyu and Jiang, Cells, 2022, 11 (22), 3549. Marullo et al., ACS Pharmacol. Transl. Sci., 2020, 3 (2), 171–178. McCormack et al., Phys. Rev., 70:391-425, 1990. McCuller et al., StatPearls Publishing: Treasure Island (FL), 2023. Mishra et al., Chem. Rev., 100:1973–2012, 2000. Molgó et al., Biol. Res., 2004, 37 (4), 635–639. Mustroph, Phys. Sci. Rev, https://doi.org/10.1515/psr-2020-0145, 2021. Mustroph & Towns, ChemPhysChem, 19:1016–23, 2018. Pchitskaya et al., Cell Calc., 70:87-94, 2018. Pollard et al., Adv. Funct. Mater., 2007, 17 (5), 718–729. Reiken et al., J. Cell Biol., 2003, 160 (6), 919–928. Roke et al., Proc. Natl. Acad. Sci., 2018, 115 (38), 9423–9431. Sanderson et al., Cell Regul., 1990, 1 (8), 585–596. Santos et al., Adv. Sci., 2023, 10 (10), 2205781. Santos et al., Sci. Adv., 2022, 8 (22). Schmid & Salathe, Biol. Cell, 103:159–169, 2011. Screaton et al., Cell, 119:61–74, 2004. Shi et al., J. Biomed. Opt., 21:050901, 2016. Sinnecker & Schaefer, Cell Calc., 35:29–38, 2004. Stahl and Wermuth eds., Verlag Helvetica Chimica Acta, 2002. Tsutsumi et al., Cell Tissue Res., 2009, 338 (1), 99–106. Tsutsumi et al., Cell Tissue Res., 338:99–106, 2009. Wang et al., bioRxiv, 2020. Watson and Cockroft, Chem. Soc. Rev., 2016, 45 (22), 6118–6129. Wilkinson et al., Ageing Res. Rev., 2018, 47, 123–132. Xu et al., Cell, 173:762-775, 2018. Yaffe and Saxel, Nature, 1977, 270 (5639), 725–727. Zheng et al., Nat. Commun., 2021, 12 (1), 3580. Zheng et al., Nat. Commun., 12:3580, 2021. Zhu et al., APL Bioeng., 2020, 4 (1).