Role of glycocalyx in attenuation of shear stress on endothelial cells: From in vivo experiments to microfluidic circuits

摘要

Shear stress generated by blood flow is transmitted to endothelial cells lining blood vessels through the cell free layer at the blood/vessel interface, consisting of a blood plasma zone and the glycocalyx, a gel-like lining of the endothelium, composed of polysaccharides attached to the cell wall. This multilayered system determines how flow is sensed and converted into biochemical responses by the endothelium by mechanotransduction. Analysis of flow profiles in this system using particle velocimetry is not possible since the gel-like structure affects particle trajectories, precluding obtaining information on shear stress. Likewise using numerical simulations of flow and transport is not viable for fully resolving the mechanical effects within the glycocalyx and their transmission to the endothelial surface, and understanding how shear stress is sensed by the endothelium requires complex and expensive in vivo and in vitro experimentation. Equivalent microfluidic models/circuits would allow to explicitly study the impact of glycocalyx topology on shear stress in controlled systems at a fraction of the cost. We propose a continuum scale model that treats the glycocalyx as a porous medium with known porosity and permeability, while accounting for varying blood viscosity. The model is amenable to analytical solution for the time-averaged velocity profile within and above the glycocalyx, and its predictions match in vivo data, providing a framework to design microfluidic systems using micro patterns designed to simulate the macroscopic effects of the biological glycocalyx.