Mechanochemical coupling in muscle: Determining the relationship between myosin biochemistry, myosin structure, and muscle force

The main objectives of this thesis are to experimentally determine the relationship between myosin structures, myosin biochemical states, and force in muscle and to use the observed mechanochemical coupling in muscle to explain steady-state muscle contraction. Using electron paramagnetic resonance (EPR) of spin-labeled myosin heads, distinct myosin orientations were observed in different biochemical and physiological states. By simultaneously monitoring muscle force and EPR, the relationship between myosin conformational states, myosin biochemical states and muscle force was directly obtained. The results imply that mechanochemical coupling in muscle is described by an equation of state for the muscle system and that stead-state muscle contraction is described by a simple energy transfer equation. These models challenge the long-established deterministic powerstroke mechanism of muscle contraction and represent a new paradigm for energy transfer by motor proteins.