Cell structure control of endothelial mechanotaxis under fluid shear stress

Abstract

Endothelial cells in quiescent monolayers exhibit triphasic mechanotaxis in response to unidirectional fluid shear stress. In order to determine whether pre‐existing cell structure dictates the direction of cell migration under fluid shear stress, micropatterning strategies were implemented. Cells with polygonal shapes in center regions of wide lines (100‐200 μm) exhibited triphasic mechanotaxis similar to that in confluent monolayers, but elongated cells near the edges migrated primarily along their axis of elongation and did not undergo mechanotaxis under either parallel or perpendicular flow. When denuded areas were created perpendicular to the microlines, elongated cells migrated into the denuded area preferentially in the flow direction only after they were released from their preset elongation. Sparsely populated cells on the upstream edges of wide microlines continued migrating parallel to their major axes after onset of perpendicular flow, unlike single cells on an unpatterned surface that exhibited immediate downstream mechanotaxis. Only when their elongated structure was released after ~7 h of flow did these cells start to migrate in the flow direction. Thus, pre‐existing cell structure suppresses mechanotaxis of endothelial cells, an important mechanism for endothelial wound healing in applications such as vascular stents and bypass grafts. Supported by NIH grant HL‐071958.