Membrane Deformation of Endothelial Surface Layer Interspersed with Syndecan-4: A Molecular Dynamics Study

Abstract

The lipid membrane of endothelial cells plays a pivotal role in maintaining normal circulatory system functions. To investigate the response of the endothelial cell membrane to changes in vascular conditions, an atomistic model of the lipid membrane interspersed with Syndecan-4 core protein was established based on experimental observations and a series of molecular dynamics simulations were undertaken. The results show that flow results in continuous deformation of the lipid membrane, and the degree of membrane deformation is not in monotonic relationship with the environmental changes (either the changes in blood velocity or the alteration of the core protein configuration). An explanation for such non-monotonic relationship is provided, which agrees with previous experimental results. The elevation of the lipid membrane surface around the core protein of the endothelial glycocalyx was also observed, which can be mainly attributed to the Coulombic interactions between the biomolecules therein. The present study demonstrates that the blood flow can deform the lipid membrane directly via the interactions between water molecules and lipid membrane atoms thereby affecting mechanosensing; it also presents an additional force transmission pathway from the flow to the lipid membrane via the glycocalyx core protein, which complements previous mechanotransduction hypothesis.

Understanding the Role of Endothelial Glycocalyx in Mechanotransduction via Computational Simulation: A Mini Review

“…The MD model and force transmission mode is summarised in Figure 2. The same all-atom model for MD has also been applied to understand how the local lipid membrane around glycocalyx core proteins responds to the flow shear stress (Jiang et al, 2020a). By artificially switching off the charges of the core protein, the contributions of electrostatic and van der Waals interactions to cell membrane deformation induced by flow were quantified for the first time (Jiang et al, 2020a).…”

“…The same all-atom model for MD has also been applied to understand how the local lipid membrane around glycocalyx core proteins responds to the flow shear stress (Jiang et al, 2020a). By artificially switching off the charges of the core protein, the contributions of electrostatic and van der Waals interactions to cell membrane deformation induced by flow were quantified for the first time (Jiang et al, 2020a). The capability of isolating specific effects in MD demonstrates an important advantage of in silico experiments in exploring the mechanisms of mechanotransduction.…”

Sodium ion transport across the endothelial glycocalyx layer under electric field conditions: A molecular dynamics study

“…16 Among other findings, the role of charges in maintaining protein-lipid interactions was revealed by altering charge distributions of proteins. 18 The effects of external electric fields in a variety of applications including biosystems have been investigated using MD and reviewed recently. 19 Electric fields with physiological strengths play a pivotal role in wound healing and tissue regeneration (as reviewed in Ref.…”