Analysis of particle uptake by cells: Binding to several receptors, equilibration time, endocytosis

Computational procedures have been developed for analysis, simulation and prediction of uptake of particles, such as macromolecules, vesicles or virions by cells. The processes of uptake considered here include binding, or binding followed by endocytosis. We focused on three issues: (i) the incubation time required for reaching equilibration of binding as a function of particle and cell concentrations, and rate constants of adhesion and dissociation; (ii) the effect of endocytosis on the total uptake, the amount of particles bound to the cell surface and the time required for reaching a steady state; (iii) the determination of the parameters describing the binding when two or more types of receptor sites exist. The computational procedures have been applied to our results of liposome binding to murine macrophage-like cell line J774 cells in suspension at 4°C. In the case of phosphatidylserine/phosphatidylcholine/cholesterol liposomes we have determined the average numbers of high and low affinity binding sites per cell and the corresponding binding constants.