Cross-bridge cross-talk between force generation and radial lattice spacing


Meeting Abstract

63-1  Tuesday, Jan. 5 13:30  Cross-bridge cross-talk between force generation and radial lattice spacing WILLIAMS, CD*; SPONBERG, S; IRVING, TC; DANIEL, TL; Univ. of Washington; Georgia Inst. of Tech.; Illinois Inst. of Tech; Univ. of Washington cdave@uw.edu http://www.charlesdavidwilliams.com

Within muscle, actin and myosin filaments are arranged in a highly regular lattice. Force generation depends on actin-myosin cross-bridge formation which in turn depends on myosin diffusing across and bridging filament gaps. Alterations in filament lattice spacing change cross-bridge binding probability, and thus the force muscle generates. When large numbers of cross-bridges attach or detach as during maximal activation, it is likely that lattice spacing changes. An open question looms: does this feedback between force generation and binding regulation take place only in the most extreme of circumstances, or is it present during everyday activation? We use real-time X-ray diffraction measurements of lattice spacing, combined with work loops activated at various phase offsets to provoke altered binding timing (and thus possible altered lattice spacing regulation) within Manduca sexta flight muscle. Preliminary analysis shows that, contrary to a set of existing assumptions, lattice spacing varies within each work loop’s length oscillation by 0.5 nm. This is sufficient to alter maximal force production by up to 20% under conditions of maximal activation. What is even more interesting is that not only does lattice spacing vary with length, but the alteration of cross-bridge recruitment by changes in activation phase within the work loop modulates the length-lattice spacing relationship, retarding or advancing length change by 7% of cycle duration. This work was supported by ARO Grants W911NF-13-1-0435 and W911NF-14-1-0396.

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