sarcomere lattice geometry influences cooperative myosin binding in muscle肌节晶格几何影响合作在肌肉肌凝蛋白绑定.pdfVIP

Sarcomere Lattice Geometry Influences Cooperative Myosin Binding in Muscle 1 2 1* Bertrand C. W. Tanner , Thomas L. Daniel , Michael Regnier 1 Department of Bioengineering, University of Washington, Seattle, Washington, United States of America, 2 Department of Biology, University of Washington, Seattle, Washington, United States of America In muscle, force emerges from myosin binding with actin (forming a cross-bridge). This actomyosin binding depends upon myofilament geometry, kinetics of thin-filament Ca2þ activation, and kinetics of cross-bridge cycling. Binding occurs within a compliant network of protein filaments where there is mechanical coupling between myosins along the thick-filament backbone and between actin monomers along the thin filament. Such mechanical coupling precludes using ordinary differential equation models when examining the effects of lattice geometry, kinetics, or compliance on force production. This study uses two stochastically driven, spatially explicit models to predict levels of cross-bridge binding, force, thin-filament Ca2þ activation, and ATP utilization. One model incorporates the 2-to-1 ratio of thin to thick filaments of vertebrate striated muscle (multi-filament model), while the other comprises only one thick and one thin filament (two-filament model). Simulations comparing these models show that the multi-filament predictions of force, fractional cross-bridge binding, and cross-bridge turnover are more consistent with published experimental values. Furthermore, the values predicted by the multi-filament model are greater than those values predicted by the two-filament model. These increases are larger than the relative increase of potential inter-filament interactions in the multi-filament model versus the two-filament model. This amplification of coordinated cross-bridge binding