Mechanotransduction and the endothelial glycocalyx: Interactions with membrane and cytoskeletal proteins to transduce force

Abstract

The endothelial glycocalyx is an extracellular matrix that coats the endothelium and extends into the lumen of blood vessels, acting as a barrier between the vascular wall and blood flowing through the vessel. This positioning of the glycocalyx permits a variety of its constituents, including the major endothelial proteoglycans glypican-1 and syndecan-1, as well as the major glycosaminoglycans heparan sulfate and hyaluronic acid, to contribute to the processes of mechanosensation and subsequent mechanotransduction following such stimuli as elevated shear stress. To coordinate the vast array of processes that occur in response to physical force, the glycocalyx interacts with a plethora of membrane and cytoskeletal proteins to carry out specific signaling pathways resulting in a variety of responses of endothelial cells and, ultimately, blood vessels to mechanical force. This review focuses on proposed glycocalyx-protein relationships whereby the endothelial glycocalyx interacts with a variety of membrane and cytoskeletal proteins to transduce force into a myriad of chemical signaling pathways. The established and proposed interactions at the molecular level are discussed in context of how the glycocalyx regulates membrane/cytoskeletal protein function in the many processes of endothelial mechanotransduction.

Keywords: Cytoskeletal proteins; Endothelial glycocalyx; Ion channels; Mechanotransduction; Membrane proteins.