Upstream mechanotaxis behavior of endothelial cells

Vascular endothelial cell migration, which plays an important role in vascular remodeling, is known to be regulated by hemodynamic forces in the blood vessels. When shear stress is applied on mouse microvessel endothelial cells (bEnd.3) in vitro, cells exhibit upstream migration behavior with respect to the direction of the flow. To determine how shear stress magnitude influences mechanotaxis of the cells, endothelial cells were exposed to different magnitudes of unidirectional shear stress. While a higher flow rate reduces the speed of the motility, the horizontal component of the velocity parallel to the flow increases with the flow rate, indicating the higher alignment of cells in the direction parallel to the flow at a higher level of shear stress. In addition, cells seeded on softer substrate, whose elastic modulus is comparable to that of the blood vessels, show enhanced directional persistence when compared to those seeded on a stiffer substrate. The higher directionality accompanies increased stress fiber formation and focal adhesion turn-over, exhibiting higher mechanotaxis behavior. Therefore, the increased stiffness in the vessel may hinder the mechano-sensing mechanism of the endothelial cells, resulting in reduced mechanotaxis in response to hemodynamic shear stress. This substrate stiffness-dependent migration behavior can further elucidate the endothelial cell remodeling and wound healing in pathologically hardened vessels as well as re-endothelialization of vascular stents and grafted tissues.