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弱多价体系中受体和配体的招募以及超选择性结合无处不在的特征。

Recruitment of Receptors and Ligands in a Weakly Multivalent System with Omnipresent Signatures of Superselective Binding.

机构信息

Molecular Nanofabrication Group and Department for Molecules and Materials, MESA + Institute and Faculty of Science and Technology, University of Twente, Enschede, AE 7500, The Netherlands.

School of Integrated Circuits and Electronics, Beijing Institute of Technology, Beijing, 100081, China.

出版信息

Small. 2023 Jun;19(23):e2206596. doi: 10.1002/smll.202206596. Epub 2023 Mar 6.

DOI:10.1002/smll.202206596
PMID:36876448
Abstract

Recruitment of receptors at membrane interfaces is essential in biological recognition and uptake processes. The interactions that induce recruitment are typically weak at the level of individual interaction pairs, but are strong and selective at the level of recruited ensembles. Here, a model system is demonstrated, based on the supported lipid bilayer (SLB) that mimics the recruitment process induced by weakly multivalent interactions. The weak (mm range) histidine-nickel-nitrilotriacetate (His -NiNTA) pair is employed owing to its ease of implementation in both synthetic and biological systems. The recruitment of receptors (and ligands) induced by the binding of His -functionalized vesicles on NiNTA-terminated SLBs is investigated to identify the ligand densities necessary to achieve vesicle binding and receptor recruitment. Threshold values of ligand densities appear to occur in many binding characteristics: density of bound vesicles, size and receptor density of the contact area, and vesicle deformation. Such thresholds contrast the binding of strongly multivalent systems and constitute a clear signature of the superselective binding behavior predicted for weakly multivalent interactions. This model system provides quantitative insight into the binding valency and effects of competing energetic forces, such as deformation, depletion, and entropy cost of recruitment at different length scales.

摘要

在生物识别和摄取过程中,受体在膜界面的募集是至关重要的。在单个相互作用对的水平上,诱导募集的相互作用通常较弱,但在募集的集合体的水平上,相互作用则较强且具有选择性。在这里,展示了一个基于模拟弱多价相互作用诱导募集过程的支撑脂质双层 (SLB) 的模型系统。选择弱(mm 范围)的组氨酸-镍-亚氨基二乙酸 (His -NiNTA) 对,是因为它在合成和生物系统中都易于实现。研究了通过 His 功能化囊泡与 NiNTA 末端 SLB 结合诱导的受体(和配体)募集,以确定实现囊泡结合和受体募集所需的配体密度。配体密度的阈值似乎出现在许多结合特性中:结合囊泡的密度、接触区域的大小和受体密度,以及囊泡变形。这种阈值与强多价系统的结合形成对比,并构成了对弱多价相互作用预测的超选择性结合行为的明确特征。该模型系统提供了对结合价和竞争能量力(如变形、耗尽和募集的熵成本)的定量洞察力,这些力在不同的长度尺度上发挥作用。

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