Glycocalyx has a great impact on the accessibility of the endothelial cell membranes. Although the specific interactions play a crucial role in cross-membrane solute transport, nonspecific interactions cannot be neglected. In this work, we used computational modeling to quantify the nonspecific interactions that control the distribution of nanosized solutes across the endothelial glycocalyx. We evaluated the probabilities of various nanoparticles' passage through the luminal layer to the membrane. The calculations demonstrate that excluded volume and electrostatic interactions are decisive for the solute transport as compared with van der Waals and hydrodynamic interactions. Damaged glycocalyx models showed a relatively weak efficiency in sieving plasma solutes. We estimated the energy barriers and corresponding mean first passage times for nanoscale solute transport through the model glycocalyx.
Keywords: computer simulations; endothelial glycocalyx; lattice Boltzmann method; molecular dynamics; nanoparticles; permeability.
Endothelial glycocalyx plays multiple roles in the vascular system: it regulates vascular permeability, modulates the interactions between blood and endothelial cells and controls the shear stress produced by the blood flow. The defense it provides against nanoscale blood solutes such as viruses and nanoparticles is based on nonspecific interactions. Being a natural sieve, it also influences the delivery of medicines transported by the blood flow. In this work, using a computational study of the permeability of endothelial glycocalyx, we demonstrate that the mesh formed by glycan fibers forms an effective mechanical barrier against penetration by nanoscale solutes. We evaluate the characteristic energies and times for the penetration of solutes of various sizes through the glycocalyx and assess the role of different contributions to nanoparticle–glycocalyx interactions. The obtained results may help clarify glycocalyx dysfunction and design drug nanocarriers and other nanoparticle-based medical applications.