A cross-bridge cycle with two tension-generating steps simulates skeletal muscle mechanics

We examined whether cross-bridge cycle models with one or two tension-generating steps can account for the force-velocity relation of and tension response to length steps of frog skeletal muscle. Transition-state theory defined the strain dependence of the rate constants. The filament stiffness was non-Hookean. Models were refined against experimental data by simulated annealing and downhill simplex runs. Models with one tension-generating step were rejected, as they had a low efficiency and fitted the experimental data relatively poorly. The best model with two tension-generating steps (stroke distances 5.6 and 4.6 nm) and a cross-bridge stiffness of 1.7 pN/nm gave a good account of the experimental data. The two tensing steps allow an efficiency of up to 38% during shortening. In an isometric contraction, 54.7% of the attached heads were in a pre-tension-generating state, 44.5% of the attached heads had undergone the first tension-generating step, and only 0.8% had undergone both tension-generating steps; they bore 34%, 64%, and 2%, respectively, of the isometric tension. During slow shortening, the second tensing step made a greater contribution. During lengthening, up to 93% of the attached heads were in a pre-tension-generating state yet bore elevated tension by being dragged to high strains before detaching.