Cyclic strain modulates tubulogenesis of endothelial cells in a 3D tissue culture model

Abstract

Angiogenesis is the formation of new blood vessels from preexisting capillaries or venules. It occurs in a mechanically dynamic environment due to blood flow, but the role of hemodynamic forces in angiogenesis remains poorly understood. We have developed a unique in vitro system for the investigation of angiogenesis under cyclic strain. In this system, tubulogenesis of vascular endothelial cells in 3D collagen gels occurs under well-defined cyclic strain, which mimics blood-pressure-induced stretch. Using this system, we demonstrate that cyclic strain results in alignment of endothelial-cord-like structures perpendicular to the principal axis of stretch. Such preferential orientation was the most evident in deep and long cord-like structures. This in vitro system, along with the novel findings of strain-modulated endothelial tube morphology, enables the formation of an experimental basis for understanding the role of cyclic strain in the regulation of angiogenesis.