Responses of endothelial cells to extremely slow flows

The process of blood vessel formation is accompanied by very minimal flow in the beginning, followed by increased flow rates once the vessel develops sufficiently. Many studies have been performed for endothelial cells at shear stress levels of 0.1-60 dyn∕cm(2); however, little is known about the effect of extremely slow flows (shear stress levels of 10(-4)-10(-2) dyn∕cm(2)) that endothelial cells may experience during early blood vessel formation where flow-sensing by indirect mass transport sensing rather than through mechanoreceptor sensing mechanisms would become more important. Here, we show that extremely low flows enhance proliferation, adherens junction protein localization, and nitric oxide secretion of endothelial cells, but do not induce actin filament reorganization. The responses of endothelial cells in different flow microenvironments need more attention because increasing evidence shows that endothelial cell behaviors at the extremely slow flow regimes cannot be linearly extrapolated from observations at faster flow rates. The devices and methods described here provide a useful platform for such studies.