Membrane proteins (MPs) play key roles in cellular signaling pathways and are responsible for intercellular and intracellular interactions. Dysfunctional MPs are directly related to the pathogenesis of various diseases, and they have been exploited as one of the most sought-after targets in the pharmaceutical industry. However, working with MPs is difficult given that their amphiphilic nature requires protection from biological membrane or membrane mimetics. Polymersomes are bilayered nano-vesicles made of self-assembled block copolymers that have been widely used as cell membrane mimetics for MP reconstitution and in engineering of artificial cells. This review highlights the prevailing trend in the application of polymersomes in MP study and drug discovery. We begin with a review on the techniques for synthesis and characterization of polymersomes as well as methods of MP insertion to form proteopolymersomes. Next, we review the structural and functional analysis of the different types of MPs reconstituted in polymersomes, including membrane transport proteins, MP complexes, and membrane receptors. We then summarize the factors affecting reconstitution efficiency and the quality of reconstituted MPs for structural and functional studies. Additionally, we discuss the potential in using proteopolymersomes as platforms for high-throughput screening (HTS) in drug discovery to identify modulators of MPs. We conclude by providing future perspectives and recommendations on advancing the study of MPs and drug development using proteopolymersomes.

中文翻译：

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聚合物囊泡在膜蛋白研究和药物发现中的应用：进展、策略和展望

膜蛋白 (MP) 在细胞信号通路中起着关键作用，并负责细胞间和细胞内的相互作用。功能失调的 MPs 与各种疾病的发病机制直接相关，它们已被用作制药行业最抢手的目标之一。然而，鉴于 MP 的两亲性需要保护免受生物膜或膜模拟物的影响，因此使用 MP 很困难。聚合物囊泡是由自组装嵌段共聚物制成的双层纳米囊泡，已广泛用作 MP 重建和人工细胞工程中的细胞膜模拟物。这篇综述强调了聚合物囊泡在 MP 研究和药物发现中应用的普遍趋势。我们首先回顾了 polymersomes 的合成和表征技术以及 MP 插入形成 proteopolymersomes 的方法。接下来，我们回顾了在聚合物囊泡中重组的不同类型 MP 的结构和功能分析，包括膜转运蛋白、MP 复合物和膜受体。然后，我们总结了影响重构效率的因素以及用于结构和功能研究的重构 MP 的质量。此外，我们还讨论了在药物发现中使用蛋白聚合体作为高通量筛选 (HTS) 平台以识别 MP 调节剂的潜力。最后，我们提供了关于推进 MPs 研究和使用蛋白聚合体的药物开发的未来观点和建议。