Dubacheva, GV, Curk, T, Frenkel, D et al. (1 more author) (2019) Multivalent recognition at fluid surfaces: the interplay of receptor clustering and superselectivity. Journal of the American Chemical Society, 141 (6). pp. 2577-2588. ISSN 0002-7863
Abstract
The interaction between a biological membrane and its environment is a complex process, as it involves multivalent binding between ligand/receptor pairs, which can self-organize in patches. Any description of the specific binding of biomolecules to membranes must account for the key characteristics of multivalent binding, namely, its unique ability to discriminate sharply between high and low receptor densities (superselectivity), but also for the effect of the lateral mobility of membrane-bound receptors to cluster upon binding. Here we present an experimental model system that allows us to compare systematically the effects of multivalent interactions on fluid and immobile surfaces. A crucial feature of our model system is that it allows us to control the membrane surface chemistry, the properties of the multivalent binder, and the binding affinity. We find that multivalent probes retain their superselective binding behavior at fluid interfaces. Supported by numerical simulations, we demonstrate that, as a consequence of receptor clustering, superselective binding is enhanced and shifted to lower receptor densities at fluid interfaces. To translate our findings into a simple, predictive tool, we propose an analytical model that enables rapid predictions of how the superselective binding behavior is affected by the lateral receptor mobility as a function of the physicochemical characteristics of the multivalent probe. We believe that our model, which captures the key physical mechanisms underpinning multivalent binding to biological membranes, will greatly facilitate the rational design of nanoprobes for the superselective targeting of cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 American Chemical Society. This is an author produced version of a paper published in Journal of the American Chemical Society. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Funding Information: | Funder Grant number EU - European Union GA 306435 |
Depositing User: | Symplectic Publications |
Date Deposited: | 06 Feb 2019 14:52 |
Last Modified: | 24 Jan 2020 01:38 |
Status: | Published |
Publisher: | American Chemical Society |
Identification Number: | 10.1021/jacs.8b12553 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:142163 |