Single cardiac ventricular myosins change step-size with loading

Abstract

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. The cardiac myosin motor powers the beating heart by catalyzed ATPase free energy conversion to contractile work. Transgenic mouse models for heart disease express mouse a-cardiac myosin heavy chain with human essential light chain (ELC) in wild type (WT), or hypertrophic cardiomyopathy linked mutant forms, A57G or E143K. Mutants modify the ELC actin binding N-terminus or C-terminus regions. Motility and single myosin mechanical characteristics show stark contrasts between the motors related to their average force, power, and displacement while all indicate the ability to down-shift ensemble step-size with increasing load. A57G and E143K consume more ATP than control WT in the presence of actin with A57G upregulating and E143K downregulating power compared with WT. Higher ATP consumption and downregulated power in E143K implies a lower unitary force. Effects on power are consistent with an A57G that impairs the ELC N-terminus actin binding and an E143K that reduces lever-arm rigidity.