Glycocalyx-induced cell membrane protrusions at the cell-substrate interface

This work examines the interplay of hyaluronan-rich glycocalyx with the cell membrane and its role in generating membrane protrusions. Previous work has shown that densely grafted polymers on a cell membrane surface lead to an instability which drives the formation of micron-sized membrane protrusions. These protrusions, such as long, thin microvilli, are more sharply curved than the rest of the cell, which reduces the strength of repulsive steric and electrostatic interactions between neighboring polymers. We examine that model in the context of hyaluronan-rich glycocalyx both theoretically and experimentally. Then we extend the model to examine whether such membrane instabilities can occur at the cell-substrate interface, where growing protrusions from the membrane will encounter addition mechanical resistance arising from the compressed glycocalyx between the substrate and the cell. Understanding of the occurrence and conditions for glycocalyx-induced membrane protrusions is important for studies of cell-extracellular matrix and cell-cell interactions, in particular in the context of cell adhesion and migration and the shedding of extracellular vesicles.