Strengthening of cell-matrix adhesions in response to applied force has been well documented. However, while implied by various lines of evidence, the force-mediated strengthening of cell-cell adhesions has not been directly demonstrated. In the current study, we present results consistent with force strengthening in adherens junctions, obtained by application of different force profiles to VE-cadherin-coated magnetic beads attached to endothelial cells. When force is ramped from a low to high value over time, fewer beads detach than with the immediate application of high force. Cells treated with cytochalasin D or lacking Ena/VASP activity show similar levels of detachment relative to controls, but force strengthening is lost. Further, cells overexpressing VASP show stronger adhesion in response to low and high force, but adhesion weakening in response to ramped forces. These results indicate that force-mediated adhesion strengthening Occurs in endothelial adherens junctions and that dynamic VASP activity is necessary for this process. (C) 2008 Elsevier Inc. All rights reserved.