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Ligand-receptor binding in confined environments: from specific protein adsorption to nanoparticle attachment and drug delivery

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Ligand-receptor binding is a ubiquitous process in biology and it has been the basis for the design of biosensors and drug delivery systems. The question that we address in this presentation is what is the best way to optimize binding when the ligands and receptors are in a confined environment. This important practical question is one example of the more general problem of the effect of confinement in chemical equilibrium reactions. To understand this question we will present predictions form a molecular theoretical approach that enables us to understand the relationship between molecular organization, packing and ligand-receptor binding. Explicit comparisons with experimental observations will be shown where the predictions of the theory are in very good agreement with experimental observations. We will discuss two different scenarios. The first problem relates to the way in which the binding of proteins to surfaces and nanoparticles can be optimized using polymer molecules as spacers. The second case involves the binding of polymer-coated nanoparticles (or micelles) to surfaces. In these systems we discuss the role that surface mobility of the ligand spacers has on the binding and how this effect can be used to optimize targeted drug delivery. We will concentrate on the case in which the particles are coated with mixtures of spacers that can be used to optimize binding to specific cells. The synergetic effect of electrostatic interactions and ligand-receptor binding will be discussed in detail. The results of the theory will be summarized in terms of how to design surface coatings for surfaces and nanoparticles that optimize binding by the proper understanding of the coupling between molecular interactions, confinement and the flexibility of polymer molecules.

This talk is part of the CamBridgeSens series.

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