The influence of hemodynamic forces and intercellular interactions on endothelial cell migration
Abstract
Endothelial cell (EC) migration plays a fundamental role in a number of vascular scenarios including angiogenesis, wound healing, and re-endothelialization of vascular grafts. Hemodynamic forces from blood flow are known to mechanically regulate the migration of ECs by applying shear stresses to their apical surfaces. Much research has shown that cell migration is correlated to the level of applied shear stress, yet little has been studied on the specific effects of shear rate in modulating cell mobility. It was the aim of this study to characterize the individual contribution of these two factors on subconfluent bovine aortic ECs under steady laminar flow. Shear stress and shear rate were independently controlled by adjusting the viscosity of the culture medium, and resulting cell velocities and overall net displacements were observed. We demonstrate that cell mobility is not only modulated by shear stress but is rather a result of a combination of hemodynamic factors. More specifically, shear stress tends to regulate cell velocity, whereas shear rate guides cell movement in the direction of flow. Implications for this research are vast, as the failure of the endothelium to adapt to flow can lead to atherosclerosis or abnormal vessel repair. To understand if these trends hold true in a more physiologically-relevant environment, we also performed flow experiments on EC-smooth muscle cell co-cultures and elucidated the interplay of these cell-cell interactions in regulating flow-induced EC migration. Taken together, these findings provide insight into the contributions of the mechanical environment on vascular function and dysfunction