(142az) Response of Endothelial Cells to Stagnation Point Flows

Human blood vessels are lined with a single cell layer called the endothelium. This mechano-sensitive layer senses and responds to the hydrodynamic forces of the blood imposed upon it by the pumping action of the heart. Under conditions of steady shear stress, endothelial cells orient parallel to the direction of blood flow and provide a healthy, tight barrier that protects against vessel diseases such as atherosclerosis. 

Vascular disease occurs preferentially in locations where vessels branch or bifurcate. This geometry results in unsteady flow patterns referred to as “disturbed flow.” Specifically, stagnation points resulting from flow recirculation, combined with impinging and upwelling flows, are thought to cause an unhealthy endothelial cell layer that is prone atherosclerosis. Although the subject of intense interest, the underlying molecular mechanisms connecting disturbed flow to vascular disease remain incompletely understood.

To investigate the behavior of endothelial cells exposed to disturbed flow, we built a novel submerged impinging jet device that produces a stagnation point flow, and that allows us to observe the behavior of endothelial cells in this flow environment on the hours/days timescale. We observe dramatic changes in cell migration, orientation, and crowding as a function of Reynolds number. Our observations also reveal a remarkable ability of endothelial cells to sense and respond to spatial gradients in fluid shear. We discuss these results in the context of human physiology and disease.