Three-dimensional network formation of endothelial cells depended on shear stress

The mechanical stimulus of shear stress enhances the function of endothelial cells as well as their microvessel network formation. Using an in vitro three-dimensional (3-D) model set in a parallelplate flow chamber, we investigated the effect of shear dependency on 3-D microvessel formation. Bovine pulmonary microvascular endothelial cells (BPMECs) formed a monolayer on collagen gel and were exposed to the series of laminar shear stress (0.09-1.38 Pa) for 48 h in the presence of basic fibroblast growth factor. We found different number and spatial distribution of lamellipodia formed in the tip of the 3-D networks, which might promote the network extension. Furthermore, the morphology of the formed 3-D networks depended on the magnitude of shear stress whereas the network expansion in the horizontal plane did not. In particular, the network depth was significantly enhanced with the increasing magnitude of shear stress. These results demonstrate that the magnitude of shear stress is an important factor to control the formation of endothelial 3-D networks through lamellipodia formation.