Chemistry, Materials Science and Engineering UC Berkeley , Berkeley, California 94720, United States.
Science and Technology, Aarhus University , 8000 Aarhus, Denmark.
Biomacromolecules. 2017 Nov 13;18(11):3706-3713. doi: 10.1021/acs.biomac.7b01136. Epub 2017 Oct 9.
The ability of styrene maleic acid copolymers to dissolve lipid membranes into nanosized lipid particles is a facile method of obtaining membrane proteins in solubilized lipid discs while conserving part of their native lipid environment. While the currently used copolymers can readily extract membrane proteins in native nanodiscs, their highly disperse composition is likely to influence the dispersity of the discs as well as the extraction efficiency. In this study, reversible addition-fragmentation chain transfer was used to control the polymer architecture and dispersity of molecular weights with a high-precision. Based on Monte Carlo simulations of the polymerizations, the monomer composition was predicted and allowed a structure-function analysis of the polymer architecture, in relation to their ability to assemble into lipid nanoparticles. We show that a higher degree of control of the polymer architecture generates more homogeneous samples. We hypothesize that low dispersity copolymers, with control of polymer architecture are an ideal framework for the rational design of polymers for customized isolation and characterization of integral membrane proteins in native lipid bilayer systems.
苯乙烯-马来酸共聚物将脂质膜溶解成纳米大小的脂质颗粒的能力，是在保留部分天然脂质环境的情况下，获得可溶性脂质盘中膜蛋白的一种简便方法。虽然目前使用的共聚物可以很容易地从天然纳米盘中提取膜蛋白，但它们高度分散的组成很可能会影响圆盘的分散性和提取效率。在这项研究中，可逆加成-断裂链转移（RAFT）聚合被用来控制聚合物的结构和分子量的分散性，具有高精度。基于对聚合反应的蒙特卡罗模拟，预测了单体组成，并允许对聚合物结构与组装成脂质纳米颗粒的能力进行结构-功能分析。我们表明，对聚合物结构的更高程度的控制会产生更均匀的样品。我们假设，具有控制聚合物结构的低分散性共聚物是合理设计聚合物的理想框架，用于在天然脂质双层系统中对整体膜蛋白进行定制分离和表征。
