Simulation of detachment of specifically bound particles from surfaces by shear flow.

AUTOR(ES)

Kuo, S C

RESUMO

The receptor-mediated adhesion of cells to ligand-coated surfaces is important in many physiological and biotechnological processes. Previously, we measured the detachment of antibody-coated spheres from counter-antibody- and protein A-coated substrates using a radial-flow detachment assay and were able to relate mechanical adhesion strength to chemical binding affinity (Kuo and Lauffenburger, Biophys. J. 65:2191-2200 (1993)). In this paper, we use "adhesive dynamics" to simulate the detachment of antibody-coated hard spheres from a ligand-coated substrate. We modeled the antibody-ligand (either counter-antibody or protein A) bonds as adhesive springs. In the simulation as in the experiments, beads attach to the substrate under static conditions. Flow is then initiated, and detachment is measured by the significant displacement of previously bound particles. The model can simulate the effects of many parameters on cell detachment, including hydrodynamic stresses, receptor number, ligand density, reaction rates between receptor and ligand, and stiffness and reactive compliance of the adhesive springs. The simulations are compared with experimental detachment data, thus relating measured bead adhesion strength to molecular properties of the adhesion molecules. The simulations accurately recreated the logarithmic dependence of adhesion strength on affinity of receptor-ligand recognition, which was seen in experiments and predicted by analytic theory. In addition, we find the value of the reactive compliance, the parameter which relates the strain of a bond to its rate of breakage, that gives the best match between theory and experiment to be 0.01. Finally, we analyzed the effect of varying either the forward or reverse rate constants as different ways to achieve the same affinity, and showed that adhesion strength depends uniquely on the equilibrium affinity, not on the kinetics of binding. Given that attachment is independent of affinity, detachment and attachment are distinct adhesive phenomena.

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