Sensitivity of small myosin II ensembles from different isoforms to mechanical load and ATP concentration

TL;DR

This study models how mechanical load and ATP levels influence the movement of small myosin II ensembles from different isoforms, revealing distinct behaviors relevant to muscle and nonmuscle cell functions.

Contribution

It provides a systematic analysis of isoform-specific responses of myosin II ensembles to load and ATP, highlighting differences in their motility and efficiency.

Findings

Skeletal and smooth muscle myosin II ensembles move only under low load and high ATP.

High load stalls or reverses ensemble movement, but lower ATP can restore forward motion.

Nonmuscle myosin II ensembles are less affected by ATP levels due to slow kinetics.

Abstract

Based on a detailed crossbridge model for individual myosin II motors, we systematically study the influence of mechanical load and adenosine triphosphate (ATP) concentration on small myosin II ensembles made from different isoforms. For skeletal and smooth muscle myosin II, which are often used in actomyosin gels that reconstitute cell contractility, fast forward movement is restricted to a small region of phase space with low mechanical load and high ATP concentration, which is also characterized by frequent ensemble detachment. At high load, these ensembles are stalled or move backwards, but forward motion can be restored by decreasing ATP concentration. In contrast, small ensembles of nonmuscle myosin II isoforms, which are found in the cytoskeleton of nonmuscle cells, are hardly affected by ATP concentration due to the slow kinetics of the bound states. For all isoforms, the thermodynamic efficiency of ensemble movement increases with decreasing ATP concentration, but this effect is weaker for the nonmuscle myosin II isoforms.