crossbridge

Crossbridge refers to the transient, force-generating connection formed between the myosin heads of thick filaments and the actin subunits of thin filaments during muscle contraction. In striated muscles (skeletal and cardiac), this interaction underpins the sliding filament mechanism, whereby thin and thick filaments slide past each other to shorten the sarcomere.

Mechanism: The cycle begins when Ca2+ binds to troponin C, moving tropomyosin away from myosin-binding sites on actin. A myosin head bound to ADP and Pi attaches to actin, forming a crossbridge. Release of Pi strengthens the bond and the myosin head pivots, performing the power stroke that pulls actin toward the center of the sarcomere and releases ADP. After the stroke, a new ATP binds to myosin, causing detachment from actin. ATP hydrolysis re-cocks the myosin head to its energized conformation, ready for another cycle. The cycle continues as long as Ca2+ is present and ATP is available.

Regulation and variation: In smooth muscle, cross-bridge cycling is regulated differently, via phosphorylation of the myosin light chains by myosin light-chain kinase, activated by Ca2+ and calmodulin. This allows myosin heads to interact with actin without the troponin-tropomyosin mechanism dominant in skeletal muscle. The so-called latch state can occur, enabling maintained force with reduced ATP use.

Significance: The number of attached cross-bridges and their cycling rate determine the force and velocity of contraction. Myosin ATPase activity, Ca2+ concentration, and external load influence the cycle, and disturbances in cross-bridge cycling are implicated in various muscular diseases and pharmacological targets.