Cellular response of vascular smooth muscle to mechanical stimuli

Cultured vascular smooth muscle cells (VSM) were mechanically deformed by applying an equibiaxial strain to the compliant substrate to which they were adhered. The state of strain in the cells was determined from measurements of the displacements of fluorescent microspheres attached to the cell surface. The magnitude and orientation of principal strains were found to vary spatially and temporally. Uniaxially elongated cells experienced significant strains only in the longitudinal direction. Results indicate that these cells form strong adhesions only at the ends of their lamellipodal processes. A mathematical model for the mechanics of cell deformation was developed to investigate the influences of contractile force generation, viscoelasticity, and regionally varying mechanical properties and geometry on the time-dependence and regional variation of cell strain and the rate dependence of lamellipod detachment. The physiologic an pathophysiologic responses of vascular smooth muscle cells to trauma were investigated by applying strain impulses to cells in culture. Elevation of intracellular calcium and cell contraction were produced by applied strains of 10-30% at strain rates of 10-30 s$\sp{-1}$. Various degrees of cell injury manifested by localized cell swelling (blebs) were also produced. Blebs appeared within 10 seconds of the impulse. In a mild injury, the blebs were spontaneously reabsorbed within one minute. Severe injury led to uncontrolled cell swelling associated with the accumulation of intracellular calcium. These experiments represent the first cell-culture model for mechanically-induced vasospasm and cellular injury