Mechanics of Glycoprotein Organization in the Glycocalyx

Abstract

In living systems, proteins and carbohydrates called glycans are concentrated on the cell surface in a complex structure called the glycocalyx. The glycocalyx includes cell surface receptors essential for interrogating the biophysical and biochemical landscape of the local microenvironment. How forces imposed on the glycocalyx influence the diffusion, arrangement, and signaling of receptors is largely unknown. Towards the goal of illuminating the complex biomaterial that is the glycocalyx, we developed a physical model that describes the mechanics of its load-bearing glycoproteins and applied our model to predict the equilibrium response to mechanical forces from the microenvironment. The model consists of long, stiff glycoproteins, the cell membrane, and the cortical cytoskeleton network. We model the glycocalyx as a continuum of glycoproteins embedded, yet able to migrate laterally, in the membrane, where each glycoprotein is modeled as a structural beam. We consider the cytoskeleton to transmit compression from the cell body to the glycocalyx by pushing on the membrane. Force and moment balances for large bending deformations of individual elements in the model yield governing equations, which are simulated in a coupled manner along with a potential-energy dependent Boltzmann distribution for glycoprotein concentration to predict the mechanical response of the glycocalyx. We predict that the glycocalyx is able to sustain substantial pressures without significant deformations, but above a critical pressure it experiences a pressure-sensitive collapse. The critical pressure for collapse increases with the stiffness of glycoproteins and with the glycoprotein density. Furthermore, we predict the formation of load-bearing clusters of glycoproteins in energetically-favorable regions away from the cytoskeleton. Together, our results demonstrate how the bulk material properties of the glycocalyx emerge from the physical properties of its molecular constituents. The understanding that we develop has broad relevance in cell adhesion, cell-cell contact, and juxtacrine signaling.