Nathan Sniadecki, Ph.D.
Department of Mechanical Engineering
E-mail: nsniadec@uw...


TITLE:

"Endothelial Mechanobiology: Pulling Together Tightly under Shear Flow"


ABSTRACT:

Endothelial cells line the inner surface of blood vessels and form a tightly-knit monolayer that acts as a barrier to keep blood and its constituents from leaking into the vessel wall. Shear stress from blood flow can stimulate mechanotransduction in endothelial cells, which in turn changes their biomechanics and barrier function. In my talk, I will present my lab?s recent work on endothelial mechanobiology using a novel shear flow chamber with microposts. Endothelial cells were cultured on arrays of microposts and subjected to laminar or disturbed flow. We found that laminar flow increased cytoskeletal tension and adherens junction size in the cells, while disturbed flow caused lower cytoskeletal tension and reduced adherens junction size. Decreasing cytoskeletal tension with Y-27632 reduced the size of their adherens junctions, while increasing tension through Calyculin-A increased their size. Furthermore, we developed a novel method to measure intercellular forces between endothelial cells and found that intercellular forces were significantly higher for laminar flow than for static or disturbed conditions. The size of adherens junctions and tight junctions in the endothelial cells matched closely with the changes in their intercellular forces for laminar flow. Our results indicate that shear flow influences intercellular tension in endothelial monolayer, which subsequently affects the assembly of their cell-cell junctions. These findings provide deeper insight into the mechanobiology of endothelial cells and the role of shear stress in atherosclerosis and vascular surgery.