Fu Jianmian, Wang Bin, Zhu Weiping, Xu Yufang, Qian Xuhong, Yang Yangyang
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China.
Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. China.
J Mater Chem B. 2025 Jan 22;13(4):1395-1402. doi: 10.1039/d4tb01670j.
Intracellular macromolecules have the ability to form membraneless compartments, such as vacuoles and hollow condensates, through liquid-liquid phase separation (LLPS) in order to adapt to changes in their environment. The development of artificial non-homogeneous compartments, such as multiphase hollow or multicavity condensates, has gained significant attention due to their potential to uncover the mechanisms underlying the formation of artificial condensates and biomolecular condensates. However, the complexity of design and construction has hindered progress, particularly in creating dynamic non-homogeneous compartments. In this study, we present a dynamic membraneless compartment using peptide-oligonucleotide conjugates derived from short elastin-like polypeptides (sELP-ONs), which undergo pH-mediated phase transition. Below pH 8.8, the microcompartment exists as microdroplets that transform into non-homogeneous hollow condensates above pH 8.8. Notably, these hollow condensates retain liquid properties and high molecular ordering, and effectively sequester guest molecules with a hollow condensed layer. Furthermore, our sELP-ON microcompartments exhibit a feedback-induced phase transition in response to environmental pH fluctuations generated by complex enzymatic reactions mimicking cellular metabolism, providing a novel dynamic model for creating biomimetic membraneless compartments.
细胞内的大分子能够通过液-液相分离（LLPS）形成无膜区室，如液泡和中空凝聚物，以适应环境变化。人工非均相区室的发展，如多相中空或多腔凝聚物，因其揭示人工凝聚物和生物分子凝聚物形成机制的潜力而备受关注。然而，设计和构建的复杂性阻碍了进展，特别是在创建动态非均相区室方面。在本研究中，我们展示了一种使用源自短弹性蛋白样多肽（sELP-ONs）的肽-寡核苷酸缀合物的动态无膜区室，其经历pH介导的相变。在pH 8.8以下，微区室以微滴形式存在，在pH 8.8以上转变为非均相中空凝聚物。值得注意的是，这些中空凝聚物保留液体性质和高分子有序性，并通过中空凝聚层有效地隔离客体分子。此外，我们的sELP-ON微区室在模拟细胞代谢的复杂酶促反应产生的环境pH波动响应中表现出反馈诱导的相变，为创建仿生无膜区室提供了一种新型动态模型。
