Strain rate mechanotransduction in aligned human vascular smooth muscle cells

Vascular smooth muscle cells (VSMCs) exist in a dynamic mechanical environment and can sense and respond to mechanical stimuli in vivo. Stretch is known to stimulate intracellular biochemical events, but the influence of the rate at which stretch is applied has not been extensively investigated. Also, most studies of VSMC mechanotransduction use cell culture models not aligned in the direction of stretch. We aligned human VSMC in the direction of uniaxial stretch to examine the importance of strain rate and cell orientation. We demonstrate strain rate profoundly affects stretch-induced phosphorylation of extracellular signal-regulated kinase (ERK)1/2. Low strain rate induced dephosphorylation while physiologic and high rates increased phosphorylation. Dephosphorylation at low strain rate was dependent on cell orientation matching the strain field. Pretreatment with GDPbetaS indicated G proteins are required for ERK1/2 phosphorylation at physiologic strain rate. Apyrase addition to scavenge extracellular ATP inhibited ERK1/2 regulation at low and physiologic strain rates. These results indicate strain rate and cell orientation are important components of mechanotransduction.