The role of receptor uniformity in multivalent binding

Multivalency is prevalent in various biological systems and applications due to the superselectivity that arises from the cooperativity of multivalent binding. Traditionally, it was thought that weaker individual binding would improve the selectivity in multivalent targeting. Here, using analytical...

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Main Authors: Xia, Xiuyang, Zhang, Ge, Ciamarra, Pica Massimo, Jiao, Yang, Ni, Ran
Other Authors: School of Chemistry, Chemical Engineering and Biotechnology
Format: Journal Article
Language:English
Published: 2023
Subjects:
Online Access:https://hdl.handle.net/10356/169307
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author Xia, Xiuyang
Zhang, Ge
Ciamarra, Pica Massimo
Jiao, Yang
Ni, Ran
author2 School of Chemistry, Chemical Engineering and Biotechnology
author_facet School of Chemistry, Chemical Engineering and Biotechnology
Xia, Xiuyang
Zhang, Ge
Ciamarra, Pica Massimo
Jiao, Yang
Ni, Ran
author_sort Xia, Xiuyang
collection NTU
description Multivalency is prevalent in various biological systems and applications due to the superselectivity that arises from the cooperativity of multivalent binding. Traditionally, it was thought that weaker individual binding would improve the selectivity in multivalent targeting. Here, using analytical mean field theory and Monte Carlo simulations, we discover that, for receptors that are highly uniformly distributed, the highest selectivity occurs at an intermediate binding energy and can be significantly greater than the weak binding limit. This is caused by an exponential relationship between the bound fraction and receptor concentration, which is influenced by both the strength and combinatorial entropy of binding. Our findings not only provide new guidelines for the rational design of biosensors using multivalent nanoparticles but also introduce a new perspective in understanding biological processes involving multivalency.
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spelling ntu-10356/1693072023-07-14T15:31:40Z The role of receptor uniformity in multivalent binding Xia, Xiuyang Zhang, Ge Ciamarra, Pica Massimo Jiao, Yang Ni, Ran School of Chemistry, Chemical Engineering and Biotechnology School of Physical and Mathematical Sciences Engineering::Chemical engineering Engineering::Bioengineering Multivalent Nanoparticle Binding Superselectivity Multivalency is prevalent in various biological systems and applications due to the superselectivity that arises from the cooperativity of multivalent binding. Traditionally, it was thought that weaker individual binding would improve the selectivity in multivalent targeting. Here, using analytical mean field theory and Monte Carlo simulations, we discover that, for receptors that are highly uniformly distributed, the highest selectivity occurs at an intermediate binding energy and can be significantly greater than the weak binding limit. This is caused by an exponential relationship between the bound fraction and receptor concentration, which is influenced by both the strength and combinatorial entropy of binding. Our findings not only provide new guidelines for the rational design of biosensors using multivalent nanoparticles but also introduce a new perspective in understanding biological processes involving multivalency. Ministry of Education (MOE) Published version This work is supported by the Academic Research Fund from Singapore Ministry of Education Tier 1 Gant (RG59/21) and Tier 2 Grant (MOE2019-T2-2-010). 2023-07-12T00:51:22Z 2023-07-12T00:51:22Z 2023 Journal Article Xia, X., Zhang, G., Ciamarra, P. M., Jiao, Y. & Ni, R. (2023). The role of receptor uniformity in multivalent binding. JACS Au, 3(5), 1385-1391. https://dx.doi.org/10.1021/jacsau.3c00052 2691-3704 https://hdl.handle.net/10356/169307 10.1021/jacsau.3c00052 37234107 2-s2.0-85154556771 5 3 1385 1391 en RG59/21 MOE2019-T2-2-010 JACS Au © 2023 The Authors. Published by American Chemical Society. This is an open access article distributed under the terms of the Creative Commons Attribution License. application/pdf
spellingShingle Engineering::Chemical engineering
Engineering::Bioengineering
Multivalent Nanoparticle Binding
Superselectivity
Xia, Xiuyang
Zhang, Ge
Ciamarra, Pica Massimo
Jiao, Yang
Ni, Ran
The role of receptor uniformity in multivalent binding
title The role of receptor uniformity in multivalent binding
title_full The role of receptor uniformity in multivalent binding
title_fullStr The role of receptor uniformity in multivalent binding
title_full_unstemmed The role of receptor uniformity in multivalent binding
title_short The role of receptor uniformity in multivalent binding
title_sort role of receptor uniformity in multivalent binding
topic Engineering::Chemical engineering
Engineering::Bioengineering
Multivalent Nanoparticle Binding
Superselectivity
url https://hdl.handle.net/10356/169307
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