Equilibrium Structure and Mechanics of the Cellular Glycocalyx

Abstract

Cells can employ distinct modes of cell migration, ranging from mesenchymal-like or amoeboid-like single cell motility to collective migration. Each mode is characterized by a unique balance of cell-matrix and cell-cell adhesion. Carbohydrates called glycans are concentrated on the cell surface in a complex structure called the glycocalyx. While the glycocalyx is known to impede cell adhesion by acting as a steric barrier, the mechanical response of the glycocalyx and its molecular constituents to force is largely unknown. Therefore, we have developed a physical model of the glycocalyx to understand and predict its deformation and reorganization under compressive loads, such as those that would be experienced by cells in confined three-dimensional environments. Simulations of our model predict that the glycocalyx can sustain substantial pressures without undergoing significant deformations, but beyond a critical pressure it experiences a pressure-sensitive response, followed by increased resistance at high strains. This suggests that cells could switch between weakly adherent and highly adherent states depending on the degree of confinement and the compression of the glycocalyx. Additionally, the simulations predict the formation of load-bearing clusters of glycoproteins in favorable regions away from the cytoskeletal membrane attachments. We elucidate the effects of the biophysical properties of the glycocalyx and the cell membrane on the mechanical behavior. Increasing the stiffness and the density of glycoproteins and the membrane bending modulus and the cytoskeletal density or decreasing the glycoprotein length increases the collective stiffness of the glycocalyx and the pressure required to generate significant deformations. Together, our results demonstrate how bulk material properties of the glycocalyx emerge from the physical properties of its molecular constituents and how these constituents rearrange under load. The understanding developed here has broad relevance in cell migration, adhesion, communication, and other receptor-mediated processes in the glycocalyx.