Actomyosin ADP-States, Non-Hyperbolic Force-Velocity Relation and Processivity of Myosin II in Fast Skeletal Muscle

Abstract

The force-velocity relation of striated muscle is incompletely understood with respect to the molecular basis for the maximum shortening velocity and for the non-hyperbolic shape at high forces (low velocities). These, and related issues, are here elucidated using a four-state actomyosin cross-bridge model. Exploration of the parameter space of the model suggests that an actomyosin-ADP state (AM∗ADP) with a closed nucleotide pocket, or rather the strain-dependent transition out of this state, has a pivotal role in influencing both the maximum shortening velocity and the shape of the force-velocity relation in the high-force region. Another model property that influences the shape of the high-force region is the detailed dependence of cross-bridge attachment rate on cross-bridge strain. Here, the modelling results argue against ideas of high attachment rate for highly strained cross-bridges. Finally, evidence is presented that actin attached myosin heads (in the AM∗ADP state) have the appropriate structural and kinetic properties to position the partner head for rapid attachment to the next site along the actin filament. This would be reminiscent of the role of the corresponding state of myosin V and could form the basis for limited processivity of muscle myosin II to increase the power output during shortening against intermediate loads.