The Effect of Cellular Receptor Diffusion on Receptor-Mediated Viral Binding Using Brownian Adhesive Dynamics (BRAD) Simulations
Brownian adhesive dynamics (BRAD) is a new method for simulating the attachment of viruses to cell surfaces. In BRAD, the motion of the virus is subject to stochastic bond formation and breakage, and thermal motion owing to collisions from the solvent. In the model, the virus is approximated as a rigid sphere and the cell surface is approximated as a rigid plane coated with receptors. In this article, we extend BRAD to allow for the mobility of receptors in the plane of the membrane, both before and after they are ligated by viral attachment proteins. Allowing the proteins to move within the membrane produced several differences in behavior from when the receptors are immobilized. First, the mean steady-state bond number is unaffected by changes in cellular receptor density because proteins are now free to diffuse into the contact area, and the extent of binding is dictated by the availability of viral attachment proteins. Second, the time required to reach steady-state binding increases as both the cellular receptor number decreases and the receptor mobility decreases. This is because receptor diffusion is a slower process than the binding kinetics of the proteins. Decreasing the rate of protein binding was found to decrease the fraction of viruses bound to steady state, but not the extent of binding for those viruses that were bound. Increasing the binding rate increased the fraction of viruses bound, until no further viruses could bind. Alterations in receptor binding kinetics had no discernable effect on the mean steady-state bond number between virus and cell, because interactions were of sufficiently high affinity that all available receptor-viral attachment proteins were destined to bind at steady state.
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Reprinted from Biophysical Journal, Volume 86, Issue 1, January 2004, pages 272-284. Publisher URL: http://www.biophysj.org/cgi/reprint/86/1/272