Cell spreading and lamellipodial extension rate is regulated by membrane tension

Cell spreading and motility require the extension of the plasma membrane in association with the assembly of actin, In vitro, extension must overcome resistance from tension within the plasma membrane. We report here that the addition of either amphiphilic compounds or fluorescent lipids that expand ed the plasma membrane increased the rate of cell spreading and lamellipodi al extension, stimulated new lamellipodial extensions, and caused a decreas e in the apparent membrane tension. Further, in PDGF-stimulated motility, t he increase in the lamellipodial extension rate was associated with a decre ase in the apparent membrane tension and decreased membrane-cytoskeleton ad hesion through phosphatidylinositol diphosphate hydrolysis. Conversely, whe n membrane tension was increased by osmotically swelling cells, the extensi on rate decreased. Therefore, we suggest that the lamellipodial extension p rocess can be activated by a physical signal (perhaps secondarily), and the rate of extension is directly dependent upon the tension in the plasma mem brane. Quantitative analysis shows that the lamellipodial extension rate is inversely correlated with the apparent membrane tension. These studies des cribe a physical chemical mechanism involving changes in membrane-cytoskele ton adhesion through phosphatidylinositol 4,5-biphosphate-protein interacti ons for modulating and stimulating the biochemical processes that power lam ellipodial extension.