Adhesion mediated by bonds in series

Cell adhesion in physiological situations and biotechnological applications is often mediated through serial protein/protein linkages. The adhesion strength of cell/substrate contacts through receptor/ligand bonds in series is explored with a simple mathematical model and quantified with an experimental adhesion assay. A deterministic, mass-action model is developed to describe the attachment and detachment of cell/substrate contacts through single and serial bonds. The experimental system is comprised of protein-coated beads, soluble antibody linkers, and an antibody-coated glass surface. Using the Radial-Flow Detachment Assay, the adhesion strengths of bead/substrate contacts through single and serial linkages are measured. Taken together, this work shows that the specific adhesion strength of the cell/substrate contacts comprised of two receptor/ligand bonds in series is less than the specific adhesion strength of the cell/substrate contacts comprised of either of the bonds separately. In addition, the force to rupture contacts comprised of bonds in series varies with the concentration of the solution linker. The model predicts that the locus of linkage fracture location has only a mild dependence on the ratio of relative bond affinities.