Cell adhesion. Competition between nonspecific repulsion and specific bonding.

Abstract

We develop a thermodynamic calculus for the modeling of cell adhesion. By means of this approach, we are able to compute the end results of competition between the formation of specific macromolecular bridges and nonspecific repulsion arising from electrostatic forces and osmotic (steric stabilization) forces. Using this calculus also allows us to derive in a straightforward manner the effects of cell deformability, the Young's modulus for stretching of bridges, diffusional mobility of receptors, heterogeneity of receptors, variation in receptor number, and the strength of receptor-receptor binding. The major insight that results from our analysis concerns the existence and characteristics of two phase transitions corresponding, respectively, to the onset of stable cell adhesion and to the onset of maximum cell-cell or cell-substrate contact. We are also able to make detailed predictions of the equilibrium contact area, equilibrium number of bridges, and the cell-cell or cell-substrate separation distance. We illustrate how our approach can be used to improve the analysis of experimental data, by means of two concrete examples.