Two New Types of Polymer Nanodiscs for Membrane Protein Studies
Two New Types of Polymer Nanodiscs for Membrane Protein Studies
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用于膜蛋白研究的两种新型聚合物纳米圆盘
DOI：
10.1016/j.bpj.2018.11.2016
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发表时间：
2019
影响因子：
3.4
通讯作者：
Liang, Hongjun
中科院分区：
文献类型：
--
作者：
Fiori, Mariana C.;Jiang, Yunjiang;Zheng, Wan;Anzaldua, Miguel;Borgnia, Mario J.;Altenberg, Guillermo A.;Liang, Hongjun
脂质纳米盘(LND)是由膜支架蛋白(MSP)形成的带包裹的脂质双层膜补片组成的盘状纳米结构。苯乙烯-马来酸(SMA)共聚物也被用于MPS的增溶和重组为纳米盘。这些聚合物包裹的纳米盘(SMALP，用于SMA脂质颗粒)是在近生理环境中研究膜蛋白(MPS)的有前景的平台，而无需使用洗涤剂。SMA可用的共聚物的一个缺点是它们的缓冲液兼容性和灵活性有限，适用于各种应用。此外，脂质双层的流动性和稳定性破坏了用于生物技术和生物医学应用的纳米盘的发展。在这里，我们解决了SMALP和LND的一些缺点，使用了一组新的嵌段共聚物来取代MSP，并使用另一组嵌段共聚物来取代脂质双层。我们的新系列两性离子苯乙烯-马来酸衍生物共聚物(ZSMA)不像商业SMA那样在低pH值或多价阳离子存在下聚集，可用于溶解MPS并生产尺寸可控的纳米盘。我们还提供了不同zSMA共聚物的增溶能力的数据，为开发新的zSMA奠定了基础。最后，我们介绍了聚合物纳米盘(PND)作为盘状的两亲嵌段共聚物膜贴片，它比LND更稳定，易于化学修饰。我们能够用不同的共聚物制备PND，包括以聚苯乙烯为疏水核的PND。我们预计，嵌段共聚物膜的更高的机械和化学稳定性以及它们的化学通用性将为基于重组的MPS或涉及药物靶向和给药的应用打开新的机会。这项工作得到了美国国家科学基金会的DMR-1623241和CBET-1623240赠款的部分支持。
Lipid nanodiscs (LNDs) are discoidal nanostructures consisting of a lipid bilayer membrane patch encased by a belt formed by membrane scaffold proteins (MSPs). Styrene-maleic acid (SMA) copolymers have also been used for solubilization and reconstitution of MPs into nanodiscs. These polymer-encased nanodiscs (SMALPs, for SMA lipid particles) are promising platforms for studies of membrane proteins (MPs) in a near-physiologic environment without the use of detergents. One drawback of SMA available copolymers is their limited buffer compatibility and flexibility for various applications. In addition, the development of nanodiscs for biotechnology and biomedical applications is undermined by the fluidic and labile nature of the lipid bilayer. Here, we address some of the drawbacks of SMALPs and LNDs by using a set of new block copolymers to replace the MSPs and another set of block copolymers to replace the lipid bilayer. Our new family of zwitterionic styrene-maleic acid-derivative copolymers (zSMAs) does not aggregate at low pH or in the presence of polyvalent cations (as commercial SMAs do), and can be used to solubilize MPs and produce nanodiscs of controlled sizes. We also present data on the solubilization capability of different zSMA copolymers that sets the bases for the development of new zSMAs. Finally, we introduce polymer nanodiscs (PNDs) as discoidal amphiphilic block copolymer membrane patches encased by MSPs, which are more stable than LNDs and amenable for chemical modification. We were able to produce PNDs with different copolymers, including PNDs with an hydrophobic core based on polystyrene. We expect that the higher mechanical and chemical stability of block copolymer membranes and their chemical versatility will open new opportunities for applications built on the reconstituted MPs, or involved with drug targeting and delivery. This work was supported in part by NSF grants DMR-1623241 and CBET-1623240.