Cooperativity of myosin molecules through strain-dependent chemistry

There is mounting evidence that the myosin head domain contains a lever arm which amplifies small structural changes that occur at the nucleotide-bind ing site. The mechanical work associated with movement of the lever affects the rates at which the products of ATP hydrolysis are released. During mus cle contraction, this strain-dependent chemistry leads to cooperativity of the myosin molecules within a thick filament. Two aspects of cooperative ac tion are discussed, in the context of a simple stochastic model. ii! A mode st motion of the lever arm on ADP release can serve to regulate the fractio n of myosin bound to the thin filament, in order to recruit more heads at h igher loads. (ii) If the lever swings through a large angle when phosphate is released, the chemical cycles of the myosin molecules can he synchronize d at high loads. This leads to stepwise sliding of the filaments and sugges ts that the isometric condition is not a steady slate.