School of Chemistry and Chemical Engineering, Queen's University Belfast, Stranmillis Road, Belfast, BT9 5AG, U.K.
School of Chemical Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, U.K.
ACS Nano. 2023 Jun 13;17(11):10327-10336. doi: 10.1021/acsnano.3c00683. Epub 2023 May 18.
Many cell membrane functions emerge from the lateral presentation of membrane receptors. The link between the nanoscale organization of the receptors and ligand binding remains, however, mostly unclear. In this work, we applied surface molecular imprinting and utilized the phase behavior of lipid bilayers to create platforms that recapitulate the lateral organization of membrane receptors at the nanoscale. We used liposomes decorated with amphiphilic boronic acids that commonly serve as synthetic saccharide receptors and generated three lateral modes of receptor presentation─random distribution, nanoclustering, and receptor crowding─and studied their interaction with saccharides. In comparison to liposomes with randomly dispersed receptors, surface-imprinted liposomes resulted in more than a 5-fold increase in avidity. Quantifying the binding affinity and cooperativity proved that the boost was mediated by the formation of the nanoclusters rather than a local increase in the receptor concentration. In contrast, receptor crowding, despite the presence of increased local receptor concentrations, prevented multivalent oligosaccharide binding due to steric effects. The findings demonstrate the significance of nanometric aspects of receptor presentation and generation of multivalent ligands including artificial lectins for the sensitive and specific detection of glycans.
许多细胞膜功能源于膜受体的侧向呈现。然而，受体的纳米级组织与配体结合之间的联系在很大程度上仍不清楚。在这项工作中，我们应用了表面分子印迹，并利用脂质双层的相行为来创建平台，在纳米尺度上再现膜受体的侧向组织。我们使用了带有双亲硼酸的脂质体，硼酸通常作为合成糖受体，并产生了三种受体呈现的侧向模式——随机分布、纳米簇和受体拥挤，并研究了它们与糖的相互作用。与随机分布受体的脂质体相比，表面印迹脂质体的亲和力增加了 5 倍以上。定量结合亲和力和协同性证明，这种增强是通过纳米簇的形成介导的，而不是受体浓度的局部增加。相比之下，尽管受体浓度局部增加，但受体拥挤由于空间位阻效应阻止了多价寡糖的结合。这些发现表明受体呈现的纳米级方面以及包括人工凝集素在内的多价配体的生成对于糖的敏感和特异性检测具有重要意义。
