Collective Force Generator Model of Muscle Contraction

Abstract

Muscle contraction results from cyclic interactions of actin-myosin binding coupled to the catalyzed hydrolysis of ATP. Although the mechanics and kinetics of muscle myosins are well established, it is less evident how these single molecule behaviors scale up to the collective behaviors of many myosin molecules working together. We have developed a computer simulation of collective force generation by myosin molecules based on well-established kinetic and mechanical properties of single myosin molecules and use an in-vitro motility assay to test model predictions. A collective force model predicts that even in in vitro motility assays myosin heads collectively generate force in common compliant elements and at sufficiently high numbers, N, reach a stall force Consistent with our collective force model, we show that ATPase activity in a motility assay increases linearly at low myosin density, saturating with actin sliding velocities, V, at high myosin densities. We show that activation of V upon addition of inorganic phosphate, Pi, results from Pi decreasing the auto-inhibiting collective force, which in turn activates the ATPase activity. Collective force generation by myosin results in unexpected emergent mechanical behaviors that offer new interpretations for how muscle works.