Adhesion behavior of endothelial progenitor cells to endothelial cells in simple shear flow

摘要

The adhesion of endothelial progenitor cells (EPCs) on endothelial cells (ECs) is one of the critical physiological processes for the regenesis of vascular vessels and the prevention of serious cardiovascular diseases.Here,the rolling and adhesion behavior of EPCs on ECs was studied numerically.A two-dimensional numerical model was developed based on the immersed boundary method for simulating the rolling and adhesion of cells in a channel flow.The binding force arising from the catch bond of a receptor and ligand pair was modeled with stochastic Monte Carlo method and Hookean spring model.The effect of tumor necrosis factor alpha (TNF-α) on the expression of the number of adhesion molecules in ECs was analyzed experimentally.A flow chamber system with CCD camera was set up to observe the top view of the rolling of EPCs on the substrate cultivated with ECs.Numerical results prove that the adhesion of EPC on ECs is closely related to membrane stiffness of the cell and shear rate of the flow.It also suggests that the adhesion force between EPC and EC by P-selectin glycoprotein ligand-1 only is not strong enough to bond the cell onto vessel walls unless contributions of other catch bond are considered.Experimental results demonstrate that TNF-α enhanced the expressions of VCAM,ICAM,P-selectin and E-selectin in ECs,which supports the numerical results that the rolling velocity of EPC on TNF-α treated EC substrate decreases obviously compared with its velocity on the untreated one.It is found that because the adhesion is affected by both the rolling velocity and the deformability of the cell,an optimal stiffness of EPC may exist at a given shear rate of flow for achieving maximum adhesion rates.