Controlling load-dependent contractility of the heart at the single molecule level [article]

Chao Liu, Masataka Kawana, Dan Song, Kathleen M Ruppel, James Spudich
2018 bioRxiv   pre-print
Concepts in molecular tension sensing in biology are growing and have their origins in studies of muscle contraction. In the heart muscle, a key parameter of contractility is the detachment rate from actin of myosin, which determines the time that myosin is bound to actin in a force-producing state and, importantly, depends on the load (force) against which myosin works. Here, we measure the detachment rate of single molecules of human β-cardiac myosin and its load dependence. We find that both
more » ... . We find that both can be modulated by both small molecule compounds and cardiomyopathy-causing mutations. Furthermore, effects of mutations can be reversed by introducing appropriate compounds. Our results suggest that activating vs. inhibitory perturbations of cardiac myosin are discriminated by the aggregate result on duty ratio, average force, and ultimately average power output and that cardiac contractility can be controlled by tuning the load-dependent kinetics of single myosin molecules.
doi:10.1101/258020 fatcat:4uvw26hqvnc27ch4cuzbud3omu