REGULATION OF ENDOTHELIAL-CELL MORPHOGENESIS BY INTEGRINS, MECHANICALFORCES, 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 angi ogenesis in vivo. Using this model, blocking antibody studies revealed a major role for the alpha 6 beta 1 integrin in cord formation, Durin g this process, two alterations in the Matrigel structure were observe d which suggested a mechanism for the precision of cord formation. Fir st, Matrigel contracted and lifted off an agarose support and second, linear distortions became visible in the Matrigel that correspond to t he migration pathways of endothelial cell processes. These pathways, w hich we have termed ''matrix guidance pathways,'' appear to result fro m the generation of mechanical tension between endothelial cells. The above data support the concept that endothelial cell guidance during m orphogenetic events could be controlled by the ability of these cells to exert mechanical forces on the surrounding extracellular matrix to create pathways for migration. (C) 1995 Academic Press,Inc.