Molecular MotorsActivate Skeletal Muscle

Precise remote control of skeletal muscle contraction could be beneficial to the study and treatment of muscular dysfunction. Recently, we reported a method regulating intracellular calcium signaling using molecular motors (MMs), molecules that rotate submolecular components unidirectionally upon absorption of light. Here, we explore the application of this methodology to skeletal muscle tissue. Our results demonstrate that MMs induce intracellular calcium release in C2C12 myoblasts and differentiated myotubes via IP3-mediated signaling in a fashion that depends on their fast unidirectional rotation. Inhibition of proteins involved in the cAMP pathway such as adenylyl cyclase and protein kinase A also reduced the magnitude of the elicited calcium responses. We further show that, in differentiated C2C12 myotubes, the calcium signaling events driven by MM activation cause localized myotube contraction. This work demonstrates the use of a molecular mechanical technique to directly control skeletal muscle contraction, expanding the scope of available tools to study muscle contraction in a single-cell regime and treat a range of myopathies.