The Molecular Structure of the Endothelial Glycocalyx. Models to Interpret High-Resolution Imaging of an Ordered Structure for the Molecular Filter at the Microvascular Wall.

The endothelial glycocalyx is a complex fibrous network of molecules that extends from the endothelial cell membrane for distances that range from less than 0.3 micron to several microns. The mechanisms determining the overall organization of the glycocalyx are still poorly understood, but our understanding is informed by high-resolution methods to analyze periodicity in electron micrographs of the glycocalyx revealed by chemical stains, and super-resolution optical imaging of specific moieties such as heparan sulfate and hyaluronic acid. The interpretation of these images in terms of the permeability properties of the vascular wall requires additional modeling of water and macromolecule flows through ordered molecular structures. While hydrodynamic approaches have been the primary focus of these efforts, extension of the fiber matrix theories that account for the space available to water and solutes within the matrix provides new ways to interpret images where detailed hydrodynamic models are not yet available. A combination of both approaches suggests ways to evaluate the primary molecular filter formed by the spaces between fibers in the glycocalyx in two possible arrangements: Thicker 10-12 nm diameter fibers formed by the core proteins of syndecans and glypicans and their side chains with adsorbed plasma components or thinner (<2 nm diameter) fibers of glycoprotein sidechains that extend above the core protein. This chapter is dedicated to Charles Michel, whose novel experimental methods to investigate the glycocalyx in microvessels, where permeability was measured, and associated theoretical analyses are starting points for the material described in this chapter.