Amphiphilic copolymers capable of extracting membrane proteins directly from lipid bilayers into “native nanodiscs” promise a simpler membrane protein sample preparation procedure for structural and functional studies. Unfortunately, the selection of nanodisc-forming copolymers is currently limited to molecules that are heterogeneous in terms of molecular weight and monomer sequence, limiting their efficacy in extracting membrane proteins. Here, we report the development of a highly alternating copolymer composed of acrylic acid and styrene by taking advantage of the fundamental reactivity ratios of these monomers. We show that these copolymers, which we term AASTY, are effective solubilizers of membrane proteins expressed in mammalian cells by virtue of their structured amphiphilicity. These AASTY copolymers are promising alternatives to styrene-maleic acid copolymers and provide a new chemical platform for structural and functional characterization of integral membrane proteins in native nanodiscs.

能够直接从脂质双层中提取膜蛋白进入“天然纳米盘”的两亲共聚物有望为结构和功能研究提供更简单的膜蛋白样品制备方法。不幸的是，目前形成纳米盘的共聚物的选择仅限于分子量和单体序列不均一的分子，从而限制了其提取膜蛋白的功效。在这里，我们报告了利用这些单体的基本反应率，开发了一种由丙烯酸和苯乙烯组成的高度交替共聚物的过程。我们表明，这些共聚物（我们称为AASTY）凭借其结构两亲性，是在哺乳动物细胞中表达的膜蛋白的有效增溶剂。