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Ion transport through the endothelial glycocalyx layer is closely associated with many vascular diseases. Clarification of ion behaviors around the endothelial glycocalyx layer under varying circumstances will benefit pathologies related to cardiovascular and renal diseases. In this research, a series of large-scale molecular dynamics simulations are conducted to study the response of ion transport to the changing blood flow velocity and the shedding of endothelial glycocalyx sugar chains. Results indicate that blood flow promotes the outward Na +  transport from the near-membrane region to the lumen via the endothelial glycocalyx layer. Scrutiny of sugar-chain dynamics and their interactions with Na +  suggests that corner conformation of endothelial glycocalyx sugar chains confines the movement of the Na + , whereas stretching conformation facilitates the motion of Na +  ions. The flow impact on ion transport of Na +  is nonlinear. Based on the findings, the Starling principle and its revised version, which are prevailingly used to predict the ion transport of the endothelial glycocalyx layer, are further improved. An estimation based on the further revised Starling principle indicates that physiological flow changes the osmotic part of transendothelial water flux by 8% compared with the stationary situation.    NEW &amp; NOTEWORTHY The biophysical roles of negatively charged oligosaccharides of the endothelial glycocalyx have gained increasing attention due to their importance in regulating microvascular fluid exchange. The Starling principle and its revisions are at the heart of the understanding of fluid homeostasis in the periphery. Here, the blood flow changes the conformations of glycocalyx sugar chains, thereby influencing availability of Na +  for transport. Based on the findings, the Starling principle and its revision are further improved.

Microvascular ion transport through endothelial glycocalyx layer: new mechanism and improved Starling principle