Title: Biophysical Evidence for the Simple Harmonic Motion of Tropomyosin in the Regulation of Muscle Contraction
Abstract: The simple harmonic motion of tropomyosin was proposed to describe the regulatory mechanism of tropomyosin in muscle contraction (Earley, AJP, 261:C1184-95, 1991). It was suggested, in part, by the periodic distribution of charged amino acids on the outer surface of tropomyosin, indicating the nodes (no bending) and anti-nodes (maximum bending), as the amplitude of the simple harmonic motion increases, causing length to decrease, leading to the activation-associated displacement of tropomyosin into the actin groove. Experimental support was based primarily on the predicted biphasic variation of both calcium-sensitivity and maximum active tension (Po) as the thick filament electrostatic force of repulsion increases exponentially in magnitude and varies in direction as filament spacing decreases with stretch or osmotic compression. Biophysical experiments were performed to test this theory (Rayes et al, PLOS One, 6(6): e21277, 2011). Bi-functional probes at 4 locations monitored tropomyosin backbone dynamics in reconstituted ghost muscle fibers. At all 4 locations, motion decrease >1000-fold upon incorporation into fibers and decreased further upon addition of troponin, remaining largely unchanged upon addition of calcium and myosin subfragment-1. It was concluded that backbone motion of tropomyosin was unlikely to play a role in muscle contraction. However, the significance of these probes and observations with respect to predicted nodes and anti-nodes was not considered. As discussed, no probe interrogated an anti-node. Three probes interrogated nodes (no bending) and one was intermediate. The global flexibility and dynamic motion of tropomyosin is generally recognized. Consequently, detection of reduced motion or flexibility at or near predicted nodes provides biophysical evidence for the simple harmonic motion of tropomyosin in the regulation of muscle contraction and the proposed molecular basis for length-dependent regulation of active tension and Starlings law of the heart.