Glycocalyx dynamics and membrane curvature under cytosolic pressure

Abstract

ABSTRACTThe glycocalyx is a soft material composed of glycosylated proteins and lipids decorating the plasma membrane of cells. Although the glycocalyx is a mechanical conduit between the plasma membrane and the cell surroundings, the coupled dynamics of the glycocalyx and membrane are poorly understood in most cell processes. Here, we construct a dynamic model to predict the coupled mechanical behaviors of the glycocalyx and membrane due to internal cytosolic pressure in a cell interacting with an external substrate. We report how the glycocalyx constituents bear cytosolic loads, physically rearrange, and shape the cell membrane. Simulations of the model predict that highly flexible, polymeric elements in the glycocalyx are uniformly compressed in the cell-substrate contact zone. However, more rigid, fiber-like glycocalyx constituents dynamically rearrange over timescales on the order of 10 milliseconds, concentrating into clusters. This spatial heterogeneity allows close apposition of the plasma membrane with the substrate, a geometry that would be favorable for subsequent adhesive bond formation. Clustered glycocalyx constituents imprint nanotopographical features on the plasma membrane with longitudinal dimensions of 200 – 300 nm. Analysis of the membrane topographies reveals curvatures that could be sufficient to elicit biological responses through curvature sensing proteins, such as BAR-domain proteins. Together, our simulations suggest how instabilities in the compressed glycocalyx could mediate downstream adhesive and signaling processes in the bleb-substrate interface.