Abstract
The endothelial glycocalyx (EG), a sugar-rich layer that lines the luminal surface of blood vessels, is an important constituent of the vascular system. Although the chemical composition of the EG is fairly well known, there is no consensus regarding its ultrastructure. While previous experiments probed the properties of the layer at the continuum level, they did not provide sufficient insight into its molecular organisation. In this work, we investigate the EG mechanics using two simple brush and bush-like simulation models, and use these models to describe its molecular structure and elastic response to indentation. We analyse the relationship between the mechanical properties of the EG layer and several molecular parameters, including the filament bending rigidity, grafting density, and the type of ultrastructure . We show that variations in the glycan density determine the elasticity of the EG for small deformations, and that the normal stress may be effectively dampened by the EG layer, preventing the stress from being transferred to the cell membrane. Furthermore, our bush-like model allows us to evaluate the forces and energies required to overcome the mechanical resistance of the EG.
Highlights
Despite being just several hundred nanometres thick in capillaries[1], the endothelial glycocalyx (EG) has an enormous impact on a number of vascular functions, playing a major role in sieving and mechanotransduction processes, as well as in the chemical control of the endothelial cell environment
At the more coarse-grained level, the EG was modeled as a part of the endothelium complex in a one-dimensional model[25], and various methods have been employed in the numerical simulations of the atomistic and coarse-grained EG models, including Monte Carlo[26], Molecular Dynamics (MD)[24], and Dissipative Particle Dynamics methods[27]
We report on the mechanical properties of several models of the EG
Summary
Despite being just several hundred nanometres thick in capillaries[1], the endothelial glycocalyx (EG) has an enormous impact on a number of vascular functions, playing a major role in sieving and mechanotransduction processes, as well as in the chemical control of the endothelial cell environment. It has been shown experimentally that the EG can efficiently filter plasma solutes so that only the smaller molecules can penetrate it[2,3], and can effectively resist both the pressure exerted by red blood cells (RBCs)[1,4], and shear stresses exerted by the plasma While this mechanical resistance of the EG is generally attributed to the high bending rigidity of its constituent molecular fibres, experiments with cultured cells performed by Florian et al.[5], and in vivo experiments by Mochizuki[6], indicated that two cross-linking molecules—heparan sulfate and hyaluronan (constituents of the EG)—may play an important role in the detection and amplification of flow-induced shear forces. One of the crucial steps in the construction of such descriptions was made by Squire and coworkers, who used an autocorrelation technique and Fourier transforms to analyse electron micrograph images of the EG Their results suggested the hexagonal bush-like structural model of EG widely accepted today[18]. We note that we tested the consistency of our predictions following from different sets of computational and experimental data
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