Integrin Clustering Is Driven by Mechanical Resistance from the Glycocalyx and the Substrate
Figure 1
Schematics of the chemo-mechanical model of integrin dynamics.
(A) Depiction of the cell-ECM interface. Mobile integrin receptors are distributed on the bottom surface of an elastic thin plate representing the cell membrane and associated actin cortex. ECM ligand sites are randomly incorporated on the top surface of an elastic substrate. Deviation from the equilibrium separation distance between the plate and substrate are resisted by a harmonic potential representing the cellular glycocalyx. During the simulation, integrin receptors switch between inactive and active conformations, and active integrins can bind ECM ligands. Free integrins not bound to the matrix can also diffuse along the cell surface. Formation of integrin-ligand bonds can induce mechanical deformations in the plate and substrate. (B) Depiction of the lattice spring model (LSM) used to numerically calculate the stress-strain behavior in the interface. Simple cubic lattices of nodes are fit to the ECM substrate and membrane/cortex plate and all nearest and next nearest nodes in each lattice are connected by springs to represent the solid mechanics of these materials. Additional springs between the nodes in the top of the substrate and bottom of the plate are added to describe the mechanics of the glycocalyx as a simple harmonic potential. Some nodes on the top surface of the substrate LSM are designated as ligand binding sites. Integrin-ligand bonds are represented by additional spring connections between these ligand sites and the bottom of the membrane/cortex LSM.