Cross-Bridge Cycle

The cross-bridge cycle is the repeating sequence of molecular interactions between myosin and actin that generates force during muscle contraction. A cross-bridge forms when a myosin head on a thick filament attaches to actin on a thin filament. Repeated attachment, force generation, detachment, and reattachment generate force and, when mechanical conditions allow, enable the filaments to slide relative to one another .^1,2

The cycle depends on ATP. When ATP binds to a myosin head that is strongly attached to actin, myosin detaches. ATP hydrolysis to ADP and inorganic phosphate is associated with a conformational change that primes the myosin head for another interaction with actin. After myosin binds actin, release of inorganic phosphate promotes stronger binding and is closely associated with the power stroke, a structural movement of the myosin head that generates force and can move the filaments relative to each other. ADP is subsequently released, leaving myosin strongly attached until another ATP molecule binds .^1,2

In skeletal and cardiac muscle, cross-bridge cycling is regulated by calcium. When intracellular calcium rises, it binds to troponin C, causing changes in the troponin-tropomyosin system that allow myosin to interact effectively with actin. When calcium falls, tropomyosin again inhibits these interactions and cross-bridge cycling declines .^1,2

The cross-bridge cycle should not be confused with excitation-contraction coupling. Excitation-contraction coupling describes the broader process linking electrical activation of a muscle cell to changes in intracellular calcium that regulate contraction. The cross-bridge cycle is the ATP-dependent molecular process through which actin and myosin generate force .^1,2