A simple macroscopic model for the diffusion and adsorption kinetics of r‐adenovirus

The diffusion of viruses toward cells is a limiting step of the infection process. To be modeled correctly, this step must be evaluated in combination with the adsorption of the virus to the cell surface, which is a rapid but reversible step. In this paper, the recombinant adenovirus (rAd) diffusion and its adsorption to 293S cells in suspension were both measured and modeled. First, equilibrium experiments permitted to determine the number of receptors on the surface of 293S ( R T  = 3,500 cell −1 ) and the association constant ( K A  = 1.9 × 10 11 M −1 ) for rAd on these cells based on a simple monovalent adsorption model. Non‐specific binding of the virus to the cell surface was not found to be significant. Second, total virus particle degradation rates between 5.2 × 10 −3 and 4.0 × 10 −2 min −1 were measured at 37°C in culture medium, but no significant virus degradation was observed at 4°C. Third, free viral particle disappearance rates from a mixed suspension of virus and cells were measured at different virus concentrations. Experimental data were compared to a phenomenological dynamic model comprising both the diffusion and the adsorption steps. The diffusion to adsorption ratio, a fitted parameter, confirmed that the contact process of a virus with a cell is indeed diffusion controlled. However, the characteristic diffusion time constants obtained, based on a reversible adsorption model, were eightfolds smaller than those reported in the literature, based on diffusion models that assume irreversible adsorption. Biotechnol. Bioeng. 2007; 98: 239–251. © 2007 Wiley Periodicals, Inc.