Delayed phosphate release can highly improve energy efficiency of muscle contraction

While the power stroke of myosin and the release of inorganic phosphate (Pi) play crucial roles in transforming ATP's chemical energy into mechanical work across diverse biological systems, the exact temporal relationship between these events continues to be intensely debated. In this study, from a functional perspective, we computationally investigate the impact of Pi release kinetics during the power stroke on muscle contraction dynamics. By implementing a mechanics model of the sarcomere unit that comprehensively incorporates the chemomechanical cycle of individual myosin molecules, we successfully replicate a broad range of experimental observations through parameter variation. Our simulation results reveal that delayed Pi release can significantly enhance energy efficiency during muscle contraction. This work suggests that a gradual Pi release that is not directly coupled with the lever arm swing may offer a route to adjust the stability of a working myosin on the actin filament, thereby modulating the power stroke to influence muscle contraction.