The development of amphipathic polymers, including various formulations of styrene-maleic acid (SMA) copolymers, has allowed the purification of increasing sizes and complexities of biological membrane protein assemblies in native nanodiscs. However, the factors determining the sizes and shapes of the resulting bio-nano particles remain unclear. Here, we show how grafting on short alkyl amine sidechains onto the polar residues leads to a broad set of nanoparticle sizes with improved solution behavior. The solubilization of lipid vesicles occurs over a wide range of pH levels and calcium concentrations, providing utility across the physiologically relevant range of solution conditions.

Furthermore, the active SMA derivatives can contain strictly alternating monomers, which have inherently lower sequence polydispersity. Pronounced differences in the shapes of native nanoparticles were formed from Escherichia coli bacterial outer membrane containing PagP protein using methyl, ethyl and propylamine derivatives of styrene-maleic anhydride. In particular, the methylamine-substituted polymer forms smaller, monodispersed nanodiscs, while the longer alkyl derivatives form worm-like nanostructures. Thus the introduction of hydrophobicity onto the polar sidechains of amphipathic polymers has profound effects on morphology of native nanodisc, with shorter methyl moieties offering more uniformity and utility for structural biology studies.

两亲性聚合物的发展，包括苯乙烯-马来酸（SMA）共聚物的各种配方，已经可以纯化天然纳米圆盘中生物膜蛋白组件尺寸和复杂性的增加。然而，决定所得生物纳米颗粒的尺寸和形状的因素仍不清楚。在这里，我们展示了如何在短烷基胺侧链上接枝到极性残基上，从而导致具有改善的溶液行为的各种纳米颗粒尺寸。脂质囊泡的增溶发生在很宽的pH值水平和钙浓度范围内，从而在生理上与溶液条件有关的范围内提供了实用性。

此外，活性SMA衍生物可包含严格交替的单体，其固有地具有较低的序列多分散性。使用苯乙烯-马来酸酐的甲基，乙基和丙胺衍生物，由含有PagP蛋白的大肠杆菌细菌外膜形成天然纳米颗粒形状的明显差异。特别地，甲胺取代的聚合物形成较小的，单分散的纳米盘，而较长的烷基衍生物形成蠕虫状的纳米结构。因此，将疏水性引入两亲性聚合物的极性侧链上对天然纳米碟的形态具有深远的影响，较短的甲基部分为结构生物学研究提供了更高的一致性和实用性。