Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 18, Pages 5579-5584Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1500622112
Keywords
tunability; superselectivity; host-guest multivalent interactions; hyaluronan
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Funding
- Marie Curie Career Integration Grant CELLMULTIVINT [PCIG09-GA-2011-293803]
- European Research Council (ERC) [306435]
- ERC [227758]
- EPSRC [EP/I001352/1]
- Herchel Smith Fund
- Engineering and Physical Sciences Research Council [EP/I001352/1] Funding Source: researchfish
- EPSRC [EP/I001352/1] Funding Source: UKRI
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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.
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