Reciprocity in dynamics of supramolecular biosystems for the clustering of ligands and receptors

• 成果类型: Article
• 署名作者: Dhiman, Shikha; Vleugels, Marle E. J.; Post, Richard A. J.; Crippa, Martina; Cardellini, Annalisa; de Korver, Esmee; Su, Lu; Palmans, Anja R. A.; Pavan, Giovanni M.; van der Hofstad, Remco W.; Albertazzi, Lorenzo; Meijer, E. W.
• 署名单位: Eindhoven University of Technology; Eindhoven University of Technology; Johannes Gutenberg University of Mainz; Erasmus University Rotterdam; Erasmus MC; Polytechnic University of Turin; Leiden University - Excl LUMC; Leiden University; Eindhoven University of Technology; University of New South Wales Sydney; University of New South Wales Sydney
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14487
• DOI: 10.1073/pnas.2500686122
• 发表日期: 2025-09-16
• 关键词: multivalent; polymers; ORGANIZATION; mechanisms; binding

摘要

Multivalent binding and the resulting dynamical clustering of receptors and ligands are known to be key features in biological interactions. For optimizing biomaterials capable of similar dynamical features, it is essential to understand the first step of these interactions, namely the multivalent molecular recognition between ligands and cell receptors. Here, we present the reciprocal cooperation between dynamic ligands in supramolecular polymers and dynamic receptors in model cell membranes, determining molecular recognition and multivalent binding via receptor clustering. The nonlinear dependences of the ligand concentration, receptors, and their binding affinity are observed experimentally by fluorescence and superresolution fluorescence microscopies, revealing a valency-dependent clustering mode of anchoring. The mechanism is supported by stochastic modeling demonstrating that such nonlinear dependence is unlikely in the absence of any dynamics and superselectivity. Using a coarse-grained molecular model, the subtle competition between local and global entropies that controls this anchoring mechanism explains the clustering. Further investigation using single particle tracking reveals the presence of two populations of bound and unbound receptors after the clustering process. The result of this study highlights the importance of reciprocity of dynamics in supramolecular polymer and lipid membrane for recruitment, multivalent binding, and clustering, all of which are crucial elements in the design of materials capable of actively interacting with biological targets.