In Vitro Tubulogenesis of Endothelial Cells: Analysis of a Bifurcation Process Controlled by a Mechanical Switch

The formation of new blood vessels in vivo is a multistep process in which sprouting endothelial cells (ECs) form tubes with lumina, these tubes being additionally organized as capillary networks. In vitro models of tubulogenesis have been developed to investigate this highly regulated multifactorial process, with special attention paid to the determinant role of mechanical interactions between ECs and the extracellular matrix (ECM). In agreement with experimental results obtained when culturing endothelial EAhy926 cells on fibrin gels, we defined theoretical thresholds between cellular traction and active cell migration along ECM strain fields above which tubulogenesis is induced.We additionally illustrated how mechanical factors may provide long-ranged positional information signals leading to localized network formation, thus providing an alternative view to the classical approach of morphogenesis based on gradients of diffusible morphogens.