Affiliations: [a] Department of Mechanical Engineering, University College London, Torrington Place, London, UK | [b] Department of Automotive Engineering, Tsinghua University, Beijing, P.R. China
Correspondence:
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Corresponding authors: Kai H. Luo, Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, UK. E-mail: k.luo@ucl.ac.uk. Yiannis Ventikos, Department of Mechanical Engineering, University College London, Torrington Place, London WC1E 7JE, UK. E-mail: y.ventikos@ucl.ac.uk
Abstract: BACKGROUND:The endothelial glycocalyx plays a pivotal role in regulating blood flow, filtering blood components, sensing and transducing mechanical signals. These functions are intimately related to its dynamics at the molecular level. OBJECTIVE:The objective of this research is to establish the relationship between the functions of the endothelial glycocalyx and its dynamics at the molecular level. METHODS:To establish such a relationship, large-scale molecular dynamics simulations were undertaken to mimic the dynamics of the glycocalyx and its components in the presence of flow shear stresses. RESULTS:First, motions of the glycocalyx core protein and the pertinent subdomains were scrutinised. Three-directional movements of the glycocalyx core protein were observed, although the flow was imposed only in the x direction. Such an observation contributes to understanding the glycocalyx redistribution as reported in experiments. Unsynchronised motion of the core protein subdomains was also spotted, which provides an alternative explanation of macroscopic phenomena. Moreover, the dynamics, root-mean-square-deviations and conformational changes of the sugar chains were investigated. Based on the findings, an alternative force transmission pathway, the role of sugar chains, and potential influence on signalling transduction pathways were proposed and discussed. CONCLUSIONS:This study relates the functions of the glycocalyx with its microscopic dynamics, which fills a knowledge gap about the links between different scales.
