Adherent cells undergo rate softening mediated by actomyosin kinetics.

Emerging studies suggest that a wide range of chronic diseases can be linked to prior physical trauma and, in some cases, to the supraphysiological deformation rates experienced by cells during injury. However, the mechanical behavior of cells during these deformations is poorly understood. Here, we studied the strain rate-dependent mechanics of vascular smooth muscle cells over rates spanning five orders of magnitude, from physiological to supraphysiological. We find that cells deformed at increasing rates undergo substantial rate softening in tension but have no rate dependence when returned to zero strain. This reversible rate softening is mediated by actin-myosin binding kinetics. Further, we find that, at supraphysiological strain rates, cells experience actin-myosin binding-mediated disruption of contractile force and alteration of gene expression. Our results suggest a mechanism by which cells shield themselves from excessive forces through cytoskeletal relaxation that loses efficacy at high strain rates such as those experienced during mechanical trauma.