Radial Force and Lattice Spacing with Multi-Spring Crossbridge Models

Abstract

Previous spatially explicit models have used crossbridges consisting of single springs aligned to the axis of the thick and thin filaments. Such one-spring models cannot account for effects of lattice spacing or radial forces generated during axial shortening. We develop crossbridge models with multiple springs to examine how different mechanisms of crossbridge deformations affect radial forces, longitudinal forces, and the effects of changes in lattice spacing. A four-spring crossbridge (4sXB) treats the S2 region and light chain domain (LCD) as linear springs, linked to the thick filament and each other by torsional springs. Changing the rest angle of the S2/LCD linking spring models force generation via a power stroke. A two-spring crossbridge (2sXB) replicates the desired abilities of the 4sXB and is less computationally expensive. Unlike the 4sXB, the length and angle of the 2sXB's springs can be determined for any head position without iterative techniques. Both the 4sXB and the 2sXB use three state kinetics that, at resting lattice spacing, are similar to previous work, easing comparison to previous studies. In contrast to single spring crossbridges, the kinetics of the 4sXB and 2sXB change with lattice spacing. Notably, the axial offset (distance between the thick filament attachment site and myosin-binding site) at which the powerstroke becomes likely to occur varies by more than 5nm over physiological lattice spacings. Both the 4sXB and the 2sXB measure the axial and radial forces generated by during production of axial force. In a typical post-powerstroke position at resting lattice spacing, the axial forces exerted by the 4sXB and the 2sXB differ by approximately 10% while the radial forces are more divergent (differing by as much as 20%), making the choice of crossbridge a critical concern in measurements of radial force. HL65497 (MR), EB001650 (CDW).