Synergy between interstitial flow and VEGF directs capillary morphogenesis in vitro through a gradient amplification mechanism.

ABSTRACT: Cell organization is largely orchestrated by extracellular gradients of morphogenetic proteins. VEGF, an essential factor for capillary formation, is stored in the extracellular matrix, but the mechanisms by which it and other matrix-bound morphogens are mobilized to form spatial gradients are poorly understood. Here, we suggest an efficient mechanism for morphogen gradient generation by subtle biophysical forces in an in vitro model of capillary morphogenesis. Using a fibrin-bound VEGF variant that is released proteolytically to mimic the in vivo situation, we report that low levels of interstitial flow act synergistically with VEGF to drive endothelial organization, whereas each stimulus alone has very little effect. To help account for this synergy, we show how these slow flows can bias

SUBMITTER: Helm CL 

PROVIDER: S-EPMC1276047 | biostudies-literature | 2005 Nov

REPOSITORIES: biostudies-literature