External forces are increasingly recognized as major regulators of cell structure and function, yet the underlying mechanism by which cells sense force and transduce it into intracellular biochemical signals and behavioral responses (‘mechanotransduction’) is largely undetermined. To aid in the mechanistic study of mechanotransduction, we devised a novel cell stretching device that allows for quantitative control and real-time measurement of mechanical stimuli and cellular biomechanical responses. Using this device, we studied the subcellular dynamic responses of contractile force and adhesion remodeling of vascular smooth muscle cells (VSMCs) to stretch. Our data showed that VSMCs could acutely enhance their contraction to resist rapid cell deformation, but they could also allow slow adaptive inelastic cytoskeletal reorganization in response to sustained cell stretch. Our study may help elucidate the mechanotransduction system in smooth muscle cells, and thus contribute to our understanding of pressure-induced vascular disease processes.

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