Ligand binding kinetics of cell surface receptors by microfluidic displacement

Abstract

Cell Surface binding kinetics of bio-molecular interaction is of fundamental importance in advancing our understanding of numerous biological processes and developing bioengineered systems. We have adopted a displacement technique, wherein a ligand is displaced from the binding site, by an excess of a ligand analog perfused through the microchannel. The theoretical model describes transient convection and diffusion in the microchannel volume following dissociation of the ligand from the cell surface receptors. To incorporate living cell processes, the model includes cell surface receptor trafficking. The decay of eluting ligand concentration follows a mono-exponential curve for one receptor sub-type or kinetic dissociation rate constant. A numerical solution is obtained using the method of finite differences and verified with an analytical solution for the case of negligible dispersion. Results illustrate how the fluid velocity and receptor internalization rate influence the ligand concentration at the microchannel outlet. This modeling effort is expected to allow better experimental design and subsequently more accurate measurement of kinetic rate constants. © 2010 International Federation for Medical and Biological Engineering.