Molecular and cellular mechanisms of muscle contraction

Synopsis

Myosin II is a molecular motor that converts chemical energy derived from ATP hydrolysis into mechanical work, ultimately resulting in muscle contraction. When myosin attaches to actin, ATP is hydrolyzed, and inorganic phosphate (Pi) and ADP are released from its active site. These reactions are coordinated with changes in the structure of myosin, promoting the so called "power-stroke" that causes sliding of actin filaments. The general features of the myosin-actin interactions are well accepted, but there are critical issues that remain unclear, including (i) the magnitude of the myosin power stroke and the relation between Pi release and force generation, (ii) the potential cooperativity between myosin molecules and actin filaments, and between myosin molecules and thin filaments, (iii) the load dependence of force production associated with the power stroke, (iv) the mechanisms of myofibril force production and sarcomere dynamics and non-uniformity during force production. In this talk, I will summarize experiments conducted with different preparations, ranging from the single molecule to sarcomere to myofibrils, aimed to understand these critical issues.