Mechanobiology of Endothelium

Abstract

Endothelial cells (EC) line the lumen of blood and lymphatic vessels. ECs are constantly exposed to cyclic stretch, shear stresses and flow derived complex stresses and the stresses due to contact with underlying basement membrane. The aim of this study is to understand the interplay between mechanical forces in the self-organization and function of endothelial cell monolayers. For this, mechanical stimuli were given using a recently developed ‘Endothelium-on-Chip’ platform, and microscope mountable microfluidic shear device to replicate disturbed flows seen in regions of curvatures and bifurcations and generate laminar flows respectively. The effect of contact derived stresses were seen via changing the underlying elasticity and viscoelasticity of the substrate and changing the matrix composition. Do mechanical cues like flow and substrate elasticity and viscoelasticity alter the selforganization, cell proliferation and traction stresses? To answer these questions, we use interval imaging experiments on endothelial cells in the custom microfluidic platforms to investigate the role of laminar and complex flows and gels of different material properties of the underlying substrate. Preliminary experiments reveal significantly motile cells in the Endothelium-on-chip as compared to control cells. Prolonged laminar shear increasing the expression of actin and alignment of cells in the flow direction. Such studies are essential to better understand mechanotransducive processes in the physiology and pathology of the endothelium.