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Title: Mechanotransduction and ion transport of the endothelial glycocalyx : a large-scale molecular dynamics study
Author: Jiang, Xizhuo
ISNI:       0000 0004 7660 7538
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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In our vessels, the endothelial glycocalyx is the first and foremost barrier directly exposed to the blood in the lumen. The functions of the normal endothelial glycocalyx under physiological conditions are widely accepted as a physical barrier to prevent the abnormal transportation of blood components (e.g. ions, proteins, albumin and etc.) and a mechanosensor and mechanotransducer to sense and transmit mechanical signals from the blood flow to cytoplasm. In this study, a series of large-scale molecular dynamics simulations were undertaken to study atomic events of the endothelial glycocalyx layers interacting with flow. This research is a pioneer study in which flow in the physiologically relevant range is accomplished based on an atomistic model of the glycocalyx with the to-date and detailed structural information. The coupled dynamics of flow and endothelial glycocalyx show that the glycocalyx constituents swing and swirl when the flow passes by. The active motion of the glycocalyx, as a result, disturbs the flow by modifying the velocity distributions. The glycocalyx also controls the emergence of strong shear stresses. Moreover, flow regime on complex surface was proposed based on results from a series of cases with varying surface configurations and flow velocities. Based on the dynamics of subdomains of the glycocalyx core protein, mechanism for mechanotransduction of the endothelial glycocalyx was established. The force from blood flow shear stress is transmitted via a scissor-like motion alongside the bending of the core protein with an order of magnitude of 10~ 100 pN. Finally, the mechanism of flow impact on ion transport was investigated and improved Starling principle was proposed. The flow modifies sugar chain conformations and transfers momentum to ions. The conformational changes of sugar chains then affect the Na+/sugar-chain interactions. The effects of flow velocity on the interactions are non-linear. An estimation in accordance to the improved Starling principle suggests that a physiological flow changes the osmotic part of Na+ transport by 8% compared with stationary transport.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available