Contractility affects stress fiber remodeling and reorientation of endothelial cells subjected to cyclic mechanical stretching

We studied the effect of contractility on stress fiber remodeling and orientation response of human aortic endothelial cells subjected to cyclic mechanical stretching. The cells were grown on silicone membranes subjected to 10% cyclic pure uniaxial stretching in the presence or absence of 2,3 butanedione monoxime(BDM), a proven inhibitor of cellular contractility. It was found that treatment of the cells with BDM (40 mM) abolished stress fibers and blocked cell reorientation in response to cyclic stretching, indicating that contractility is required for these two cellular responses. When cells were stretched in the presence of N-acetylcysteine (NAC, 20 mM), a hydrogen peroxide (H2O2) scavenger, stress fibers were still formed and the cells reoriented-but more slowly. Specifically, compared with untreated cells, NAC treated cells after 0.5, 1, and 3 h of 10% stretching had significantly (p<0.005) less skewed orientation distributions than those of untreated cells. After the cells were treated with both NAC (20 mM) and nordihydroguaiaretic acid (NDGA, 50 M), another antioxidant, however, stress fibers were abolished and cell reorientation was completely blocked. These results indicate that reactive oxygen species (ROS), including H2O2, affect stress fiber remodeling and reorientation of endothelial cells in response to cyclic stretching. We suggest that the effect of ROS on stress fiber remodeling and cell reorientation is due to the ability of ROS to regulate cellular contractility, which is crucial for these cellular responses. (C) 2000 Biomedical Engineering Society. [S0090-6964(00)001110-7].