title: Axial and radial forces of cross-bridges depend on lattice spacing.
abstract: Nearly all mechanochemical models of the cross-bridge treat myosin as a simple linear spring arranged parallel to the contractile filaments. These single-spring models cannot account for the radial force that muscle generates (orthogonal to the long axis of the myofilaments) or the effects of changes in filament lattice spacing. We describe a more complex myosin cross-bridge model that uses multiple springs to replicate myosin's force-generating power stroke and account for the effects of lattice spacing and radial force. The four springs which comprise this model (the 4sXB) correspond to the mechanically relevant portions of myosin's structure. As occurs in vivo, the 4sXB's state-transition kinetics and force-production dynamics vary with lattice spacing. Additionally, we describe a simpler two-spring cross-bridge (2sXB) model which produces results similar to those of the 4sXB model. Unlike the 4sXB model, the 2sXB model requires no iterative techniques, making it more computationally efficient. The rate at which both multi-spring cross-bridges bind and generate force decreases as lattice spacing grows. The axial force generated by each cross-bridge as it undergoes a power stroke increases as lattice spacing grows. The radial force that a cross-bridge produces as it undergoes a power stroke varies from expansive to compressive as lattice spacing increases. Importantly, these results mirror those for intact, contracting muscle force production.
authors.affiliation: Department of Physiology and Biophysics, University of Washington, Seattle, Washington, United States of America.
authors.forename: C David
authors.initials: CD
authors.lastname: Williams
authors.forename: Michael
authors.initials: M
authors.lastname: Regnier
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Daniel
mesh_terms: D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D001696:Biomechanical Phenomena / Q000502:physiology*; D019295:Computational Biology / Q000379:methods*; D008954:Models, Biological; D056004:Molecular Dynamics Simulation; D009218:Myosins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D020836:Protein Structure, Quaternary / Q000502:physiology*; D012518:Sarcomeres / Q000502:physiology; D019415:Torque
chemical_list: D000199:Actins; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009218:Myosins