Self-Assembly of Protein-Containing Lipid-Bilayer Nanodiscs from Small-Molecule Amphiphiles,Small

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Self-Assembly of Protein-Containing Lipid-Bilayer Nanodiscs from Small-Molecule Amphiphiles
Small ( IF 13.0 ) Pub Date : 2021-10-21 , DOI: 10.1002/smll.202103603
Florian Mahler ₁ , Annette Meister ₂ , Carolyn Vargas _{1,

3,

4,

5} , Grégory Durand _{6,

7} , Sandro Keller _{1,

3,

4,

5}

Affiliation

When membrane proteins are removed from their natural environment, the quality of the membrane-solubilizing agent used is critical for preserving their native structures and functions. Nanodiscs that retain a lipid-bilayer core around membrane proteins have attracted great attention because they offer a much more native-like environment than detergent micelles. Here, two small-molecule amphiphiles with diglucose headgroups and either a hydrocarbon or a fluorocarbon hydrophobic chain are shown to directly assemble lipids and membrane proteins to form native nanodiscs rather than mixed micelles. Self-assembly of nanodiscs of increasing complexity from both defined, artificial vesicles as well as complex, cellular membranes is demonstrated. A detailed investigation of bilayer integrity and membrane-protein activity in these nanodiscs reveals gentle effects on the encapsulated bilayer core. The fluorinated amphiphile appears particularly promising because its lipophobicity results in gentle, non-perturbing interactions with the nanoscale lipid bilayer. A sequential model of nanodisc self-assembly is proposed that proceeds through perforation of the original membrane followed by saturation and complete solubilization of the bilayer. On this basis, pseudophase diagrams are established for mixtures of lipids and nanodisc-forming diglucoside amphiphiles, and the latter are used for the extraction of a broad range of membrane proteins from cellular membranes.

中文翻译：

来自小分子两亲物的含蛋白质脂质双层纳米圆盘的自组装

当膜蛋白从其自然环境中移除时，所使用的膜增溶剂的质量对于保持其天然结构和功能至关重要。在膜蛋白周围保留脂质双层核心的纳米圆盘引起了极大的关注，因为它们提供了比洗涤剂胶束更像天然的环境。在这里，两个具有二葡萄糖头基和碳氢化合物或碳氟化合物疏水链的小分子两亲物被证明可以直接组装脂质和膜蛋白以形成天然纳米圆盘而不是混合胶束。证明了从定义的人工囊泡和复杂的细胞膜中自组装越来越复杂的纳米圆盘。对这些纳米圆盘中双层完整性和膜蛋白活性的详细研究揭示了对封装的双层核心的温和影响。氟化两亲物似乎特别有前途，因为它的疏脂性导致与纳米级脂质双层温和、无干扰的相互作用。提出了纳米圆盘自组装的顺序模型，该模型通过原始膜的穿孔进行，然后是双层的饱和和完全溶解。在此基础上，建立了脂质混合物和形成纳米圆盘的二葡糖苷两亲物的假相图，后者用于从细胞膜中提取广泛的膜蛋白。氟化两亲物似乎特别有前途，因为它的疏脂性导致与纳米级脂质双层温和、无干扰的相互作用。提出了纳米圆盘自组装的顺序模型，该模型通过原始膜的穿孔进行，然后是双层的饱和和完全溶解。在此基础上，建立了脂质混合物和形成纳米圆盘的二葡糖苷两亲物的假相图，后者用于从细胞膜中提取广泛的膜蛋白。氟化两亲物似乎特别有前途，因为它的疏脂性导致与纳米级脂质双层温和、无干扰的相互作用。提出了纳米圆盘自组装的顺序模型，该模型通过原始膜的穿孔进行，然后是双层的饱和和完全溶解。在此基础上，建立了脂质混合物和形成纳米圆盘的二葡糖苷两亲物的假相图，后者用于从细胞膜中提取广泛的膜蛋白。

更新日期：2021-12-09

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