Encoding biological recognition in a bicomponent cell-membrane mimic
Encoding biological recognition in a bicomponent cell-membrane mimic
复制标题
DOI：
10.1073/pnas.1821924116
复制
发表时间：
2019-02
影响因子：
11.1
通讯作者：
César Rodriguez-Emmenegger;Qi Xiao;N. Kostina;Samuel E Sherman;K. Rahimi;Benjamin E. Partridge;Shangda Li;Dipankar Sahoo;Aracelee M. Reverón Pérez;Irene Buzzacchera;Hong Han;Meir Kerzner;I. Malhotra;M. Möller;Christopher J. Wilson;Matthew C. Good;M. Goulian;T. Baumgart;M. Klein;V. Percec
中科院分区：
文献类型：
--
作者：
César Rodriguez-Emmenegger;Qi Xiao;N. Kostina;Samuel E Sherman;K. Rahimi;Benjamin E. Partridge;Shangda Li;Dipankar Sahoo;Aracelee M. Reverón Pérez;Irene Buzzacchera;Hong Han;Meir Kerzner;I. Malhotra;M. Möller;Christopher J. Wilson;Matthew C. Good;M. Goulian;T. Baumgart;M. Klein;V. Percec
意义精液镶嵌模型的细胞膜提出了一个脂质双层的海洋，其中胆固醇，蛋白质，糖复合物，和其他成分游泳。补充这一观点，一个微隔离筏模型预测集群的组件，作为中继站的细胞内信号和贩运。然而，阐明负责细胞之间的通信和识别的糖缀合物的排列以及细胞与蛋白质的排列仍然是一个挑战。本文中，设计的树突状大分子显示出自组装成囊泡，所述囊泡用作生物膜模拟物，其外围具有受控密度的糖部分。令人惊讶的是，降低糖密度可提高糖结合蛋白的生物活性。这一发现为活性复杂软物质的设计原理提供了信息，该软物质具有在细胞生物学和纳米医学中应用的潜力。自组装树枝状大分子促进了超分子结构的周期性和准周期性阵列的发现以及由此衍生的各种功能。例子是液体准晶体和它们的近似物加上螺旋柱和球体，包括一些不考虑手性的。随后在嵌段共聚物、表面活性剂、脂质、糖脂和其他复杂分子中发现了相同的周期和准周期阵列。在这里，我们报告发现的层状和六边形周期性阵列上产生的序列定义的双组分单分散低聚物含有脂质和糖脂模拟物的囊泡表面。这些囊泡，被称为glycodendrimersomes，作为细胞膜模拟物，具有类似双组分筏的分级形态。这些纳米分离的形态减少了糖-糖相互作用，使得与糖结合蛋白的结合比糖的密集排列更强。重要的是，这提供了一种通过糖与糖结合蛋白的相互作用来编码糖的反应性的机制。观察到的糖相分离的分层阵列与层状和六边形的形态编码的生物识别是最复杂的架构中尚未发现的软物质。糖的反应性增强显示可能在材料科学和纳米医学中有应用，并有可能发展成相关技术。
Significance The seminal fluid mosaic model of the cell membranes suggests a lipid bilayer sea, in which cholesterol, proteins, glycoconjugates, and other components are swimming. Complementing this view, a microsegregated rafts model predicts clusters of components that function as relay stations for intracellular signaling and trafficking. However, elucidating the arrangement of glycoconjugates responsible for communication and recognition between cells, and cells with proteins remains a challenge. Herein, designed dendritic macromolecules are shown to self-assemble into vesicles that function as biological-membrane mimics with controlled density of sugar moieties on their periphery. Surprisingly, lowering sugar density elicits higher bioactivity to sugar-binding proteins. This finding informs a design principle for active complex soft matter with potential for applications in cellular biology and nanomedicine. Self-assembling dendrimers have facilitated the discovery of periodic and quasiperiodic arrays of supramolecular architectures and the diverse functions derived from them. Examples are liquid quasicrystals and their approximants plus helical columns and spheres, including some that disregard chirality. The same periodic and quasiperiodic arrays were subsequently found in block copolymers, surfactants, lipids, glycolipids, and other complex molecules. Here we report the discovery of lamellar and hexagonal periodic arrays on the surface of vesicles generated from sequence-defined bicomponent monodisperse oligomers containing lipid and glycolipid mimics. These vesicles, known as glycodendrimersomes, act as cell-membrane mimics with hierarchical morphologies resembling bicomponent rafts. These nanosegregated morphologies diminish sugar–sugar interactions enabling stronger binding to sugar-binding proteins than densely packed arrangements of sugars. Importantly, this provides a mechanism to encode the reactivity of sugars via their interaction with sugar-binding proteins. The observed sugar phase-separated hierarchical arrays with lamellar and hexagonal morphologies that encode biological recognition are among the most complex architectures yet discovered in soft matter. The enhanced reactivity of the sugar displays likely has applications in material science and nanomedicine, with potential to evolve into related technologies.