Regulation of Endothelial Cell Morphogenesis by Integrins, Mechanical Forces, and Matrix Guidance Pathways

Basement membrane matrix is known to induce human endothelial cells to form cord-like structures that mimic those observed during early angiogenesis in vivo. Using this model, blocking antibody studies revealed a major role for the alpha 6 beta 1 integrin in cord formation. During this process, two alterations in the Matrigel structure were observed which suggested a mechanism for the precision of cord formation. First, Matrigel contracted and lifted off an agarose support and second, linear distortions became visible in the Matrigel that correspond to the migration pathways of endothelial cell processes. These pathways, which we have termed "matrix guidance pathways," appear to result from the generation of mechanical tension between endothelial cells. The above data support the concept that endothelial cell guidance during morphogenetic events could be controlled by the ability of these cells to exert mechanical forces on the surrounding extracellular matrix to create pathways for migration.