Compliance Accelerates Relaxation in Muscle by Allowing Myosin Heads to Move Relative to Actin.

The mechanisms that limit the speed at which striated muscles relax are poorly understood. This work presents, to our knowledge, novel simulations that show that the time course of relaxation is accelerated by interfilamentary movement resulting from series compliance; force drops faster when myosin heads move relative to actin during relaxation. This insight was obtained by using cross-bridge distribution techniques to simulate the mechanical behavior of half-sarcomeres that were connected in series with springs of varying stiffness. (The springs mimic the combined effects of half-sarcomere heterogeneity and muscle's series elastic component.) Half-sarcomeres that shortened by >∼10 nm when they were activated subsequently relaxed with a biphasic profile; force initially declined slowly and approximately linearly before collapsing with a fast exponential time course. Stretches imposed during the linear phase quickened relaxation, while shortening movements prolonged the time course. These predictions are consistent with data from experiments performed by many other groups using single muscle fibers and isolated myofibrils. When half-sarcomeres were linked to stiff springs (so that they did not shorten appreciably during the simulations), force relaxed with a slow exponential time course and did not show biphasic behavior. Together, these results suggest that fast relaxation of striated muscle is an emergent property that reflects multiscale interactions within the muscle architecture. The nonlinear behavior during relaxation reflects perturbations to the dynamic coupling of regulated binding sites and cycling myosin heads that are induced by interfilamentary movement.