Direct Measurements and Modeling of Avidity and Surface Mobility in Multivalent Ligand-Receptor Binding

Targeted drug delivery relies on two physical processes: the selective binding of a therapeutic particle to receptors on a specific cell membrane, followed by transport of the particle across the membrane. In this article, we address some of the challenges in controlling the thermodynamics and dynamics of these processes by combining a simple experimental system with a statistical mechanical model. Specifically, we characterize and model ligand-receptor binding between colloidal particles and fluid lipid bilayers, as well as the surface mobility of membrane-bound particles. We show that the mobility of the receptors within the fluid membrane is key to both the thermodynamics and dynamics of binding. First, we find that the particle-membrane binding free energy---or avidity---is a strongly nonlinear function of the ligand-receptor affinity. We attribute the nonlinearity to a combination of multivalency and recruitment of fluid receptors to the binding site. Our results also suggest that partial wrapping of the bound particles by the membrane enhances avidity further. Second, we demonstrate that the lateral mobility of membrane-bound particles is also strongly influenced by the recruitment of receptors. Specifically, we find that the lateral diffusion coefficient of a membrane-bound particle is dominated by the hydrodynamic drag against the aggregate of receptors within the membrane. Therefore, while it is tempting to focus on the design of ligands that target specific receptors, our results highlight that the properties of the membrane itself---its fluidity and elasticity---are equally important in determining the binding and transport of small particles on membranes.