A vasculogenesis model based on flow-induced stresses on endothelial cells

Abstract

Vascular network formation and sustenance in both normal and pathological froms of angiogenesis has been a focus of research in developmental biology. The assembly and remodeling of vascular structures play major roles in numerous pathologies, including the angiogenesis of tumors. Endothelial morphogenesis is dependent on a number of chemical and mechanical stimuli and cell–cell signaling. To understand the nature of angiogenesis and vasculogenesis, many models have been developed to simulate these phenomena based on the defined responses of endothelial cells to these stimuli. Among the mechanical signals affecting these cells, flow-related stresses, including shear stress, play a major role in migration, elongation, attachment to the matrix and neighboring cells, and eventually the morphogenesis of vascular networks. Here, we proposed a model to describe the cellular responses to shear and tensile stress induced by fluid flow, which can describe some of the morphological behaviors observed in in vitro and in vivo studies. The lattice Boltzmann method was utilized to model the flow, and the cellular Potts model was used to simulate the cellular responses to the flow. This model is based on the hypothesis that endothelial cell binding energy to the matrix is regulated by shear stress and tensile stress acting on the attachment site and is increased by shear stress and decreased by tensile stress. It was demonstrated that these rules can predict the development of vascular networks and the sustenance of lumens and regression in the low flow regions. The results of this study can be further improved to investigate endothelial dysfunctions, such as atherosclerosis, as well as tumor angiogenesis and vascular permeability, which are directly related to the flow rate and endothelial responses to shear stresses.