Estimation of Shear Stress Values Along Endothelial Tip Cells Past the Lumen of Capillary Sprouts

Abstract

Shear stress is commonly recognized as a regulator of endothelial cell dynamics associated with angiogenesis. A full understanding of how shear stresses influence endothelial cell phenotype and function during angiogenesis requires the identification of local stress distribution along capillary sprouts. However, the actual shear stress magnitudes experienced by endothelial cells remain unknown in large part to the difficulty in experimentally measuring local velocity profiles. The objective of this study was to estimate shear stress magnitudes due to local interstitial flow along endothelial tip cells that extend past capillary sprout lumens. A computational fluid dynamics model was used to estimate flows within a blind‐ended vessel, transendothelial flow out of through the vessel wall, and flow through a perivascular space. The two dimensional axisymmetric model consisted of 4 regions: vessel lumen, vessel wall, perivascular space and interstitium. The vessel wall was assumed to be porous media with 1 μm thickness. Blood plasma was represented as an incompressible Newtonian fluid with density and viscosity equal to 1050 kg/m3 and 1.2 cp, respectfully. Model parameters and geometric dimensions were selected based on previously reported literature values. Shear stresses along the wall of the tip cell extended past the lumen were calculated for varying sprout lengths (100, 200, and 500 μm), perivascular space channel width (1, 4, and 9 μm) and sprout permeability (1×10−18 and 1×10−17 m2). For the 200 μm sprout length scenario, shear stress values ranged from 0.009 to 5 dyne/cm2. Increasing sprout length, increasing permeability and decreasing perivascular space served to increase shear stress values. These results suggest the potential for endothelial cells past the lumen of a capillary sprout to experience negligible to stimulatory shear stresses dependent on sprout wall permeability and interstitial flow pathways.