Abstract: Microfluidic Chip to Characterize the Effect of Shear Flow on Pulmonary Vascular Endothelial Cell Barrier Function

Tissue necrosis factor 𝛼 (TNF-𝛼) is an inflammatory cytokine known to decrease barrier function in endothelial cells and therefore increase vascular permeability. It is known that shear stress has an effect on endothelial barrier function and inducing steady and physiologic levels (5 dyne/cm2 in capillaries) of wall shear stress will increase barrier function while static flow (0 dyne/cm2) will decrease barrier function. The overall objective of this application is to develop a multiplexed microfluidic device that houses pulmonary endothelial cells to study the effect of shear stress on vascular barrier function. By passively controlling the wall shear stress in channels that model different vessel types (arteries, arterioles, capillaries, venules, and large veins), it is possible to characterize the permeability of endothelial cell monolayers at a physiologic range of normal wall shear stresses from 5 dyne/cm2 to 50 dyne/cm2. COMSOL simulations were performed to verify the expected shear stresses within the designed chip and to gather data that allows the visualization of a relationship between varying levels of endothelial permeability at specified wall shear stresses. By doing so, we can examine the behavior of a barrier that may emulate endothelial cells, allowing us to determine the effects of shear stress on permeability.