ADHESION MEDIATED BY BONDS IN SERIES

Cell adhesion in physiological situations and biotechnological applica tions is often mediated through serial protein/protein linkages. The a dhesion strength of cell/substrate contacts through receptor/ligand bo nds in series is explored with a simple mathematical model and quantif ied with an experimental adhesion assay. A deterministic, mass-action model is developed to describe the attachment and detachment of cell/s ubstrate contacts through single and serial bonds. The experimental sy stem is comprised of protein-coated beads, soluble antibody linkers, a nd an antibody-coated glass surface. Using the Radial-Flow Detachment Assay, the adhesion strengths of bead/substrate contacts through singl e and serial linkages are measured. Taken together, this work shows th at the specific adhesion strength of the cell/substrate contacts compr ised of two receptor/ligand bonds in series is less than the specific adhesion strength of the cell/substrate contacts comprised of either o f the bonds separately. In addition, the force to rupture contacts com prised of bonds in series varies with the concentration of the solutio n linker. The model predicts that the locus of linkage fracture locati on has only a mild dependence on the ratio of relative bond affinities .