title: Designing multivalent probes for tunable superselective targeting.
abstract: Specific targeting is common in biology and is a key challenge in nanomedicine. It was recently demonstrated that multivalent probes can selectively target surfaces with a defined density of surface binding sites. Here we show, using a combination of experiments and simulations on multivalent polymers, that such "superselective" binding can be tuned through the design of the multivalent probe, to target a desired density of binding sites. We develop an analytical model that provides simple yet quantitative predictions to tune the polymer's superselective binding properties by its molecular characteristics such as size, valency, and affinity. This work opens up a route toward the rational design of multivalent probes with defined superselective targeting properties for practical applications, and provides mechanistic insight into the regulation of multivalent interactions in biology. To illustrate this, we show how the superselective targeting of the extracellular matrix polysaccharide hyaluronan to its main cell surface receptor CD44 is controlled by the affinity of individual CD44-hyaluronan interactions.
authors.affiliation: CIC biomaGUNE, 20009 Donostia/San Sebastian, Spain; gdubacheva@cicbiomagune.es rrichter@cicbiomagune.es.
authors.forename: Galina V
authors.identifier: http://orcid.org/0000-0003-1417-5381
authors.initials: GV
authors.lastname: Dubacheva
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Tine
authors.initials: T
authors.lastname: Curk
authors.affiliation: Centre de Recherches sur les Macromolécules Végétales, CNRS, 38041 Grenoble Cedex 9, France;
authors.forename: Rachel
authors.initials: R
authors.lastname: Auzély-Velty
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, United Kingdom;
authors.forename: Daan
authors.initials: D
authors.lastname: Frenkel
authors.affiliation: CIC biomaGUNE, 20009 Donostia/San Sebastian, Spain; Université Grenoble Alpes, Departement de Chimie Moléculaire, 38041 Grenoble Cedex 9, France; CNRS, Departement de Chimie Moléculaire, 38041 Grenoble Cedex 9, France; and Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany gdubacheva@cicbiomagune.es rrichter@cicbiomagune.es.
authors.forename: Ralf P
authors.initials: RP
authors.lastname: Richter
mesh_terms: D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D004563:Electrochemistry; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008962:Models, Theoretical; D009010:Monte Carlo Method; D011108:Polymers / Q000737:chemistry; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D015203:Reproducibility of Results; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D018960:Hyaluronan Receptors; D008024:Ligands; D011108:Polymers; D011956:Receptors, Cell Surface; D047392:beta-Cyclodextrins; D006820:Hyaluronic Acid; C031215:betadex
keywords: host–guest multivalent interactions; hyaluronan; superselectivity; tunability