title: Designing super selectivity in multivalent nano-particle binding.
abstract: A key challenge in nano-science is to design ligand-coated nano-particles that can bind selectively to surfaces that display the cognate receptors above a threshold (surface) concentration. Nano-particles that bind monovalently to a target surface do not discriminate sharply between surfaces with high and low receptor coverage. In contrast, "multivalent" nano-particles that can bind to a larger number of ligands simultaneously, display regimes of "super selectivity" where the fraction of bound particles varies sharply with the receptor concentration. We present numerical simulations that show that multivalent nano-particles can be designed such that they approach the "on-off" binding behavior ideal for receptor-concentration selective targeting. We propose a simple analytical model that accounts for the super selective behavior of multivalent nano-particles. The model shows that the super selectivity is due to the fact that the number of distinct ligand-receptor binding arrangements increases in a highly nonlinear way with receptor coverage. Somewhat counterintuitively, our study shows that selectivity can be improved by making the individual ligand-receptor bonds weaker. We propose a simple rule of thumb to predict the conditions under which super selectivity can be achieved. We validate our model predictions against the Monte Carlo simulations.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Martinez-Veracoechea
authors.forename: Daan
authors.initials: D
authors.lastname: Frenkel
mesh_terms: D000327:Adsorption; D001665:Binding Sites; D003198:Computer Simulation; D016503:Drug Delivery Systems; D015195:Drug Design; D008024:Ligands; D008954:Models, Biological; D009010:Monte Carlo Method; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface