| AVS 62nd International Symposium & Exhibition | |
| Biomaterial Interfaces | Monday Sessions |
| Session BI+AS-MoA |
| Session: | Characterization of Biological and Biomaterials Surfaces (2) |
| Presenter: | Ralf Richter, CIC biomaGUNE & University Grenoble Alpes, Spain |
| Authors: | G.V. Dubacheva, CIC biomaGUNE, Spain T. Curk, University of Cambridge, UK R. Auzély-Velty, Cermav, Cnrs, France D. Frenkel, University of Cambridge, UK R.P. Richter, CIC biomaGUNE & University Grenoble Alpes, Spain |
| Correspondent: | Click to Email |
A basic requirement in biomedical research is the ability to specifically target cells and tissues. Targeting typically relies on the specific binding of a 'ligand' on a tailor-made probe to a 'receptor' on the desired cell or tissue. Conventional probes efficiently distinguish a cell surface displaying the receptor from others that do not. They exhibit limited selectivity, however, when the surfaces to be distinguished display a given receptor at different densities.
Based on theoretical arguments, it has been proposed that multivalent probes that bind several receptors simultaneously can sharply discriminate between different receptor densities. Here, we present an experimental model system that demonstrates such 'superselective' targeting. To this end, recent achievements of synthetic chemistry and surface characterization were combined to create well-defined multivalent polymers and surfaces that interact with each other through highly specific host/guest interactions. With this model system, we show that 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 in life sciences (analytics, diagnostics and therapy). It also provides mechanistic insight into the regulation of multivalent interactions in biology, notably the superselective targeting of the extracellular matrix polysaccharide hyaluronan to its main cell surface receptor CD44.