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差异相互作用决定了基于RNA的生物分子凝聚物界面处的各向异性。

Differential interactions determine anisotropies at interfaces of RNA-based biomolecular condensates.

作者信息

Erkamp Nadia A, Farag Mina, Qiu Yuanxin, Qian Daoyuan, Sneideris Tomas, Wu Tingting, Welsh Timothy J, Ausserwöger Hannes, Krug Tommy J, Chauhan Gaurav, Weitz David A, Lew Matthew D, Knowles Tuomas P J, Pappu Rohit V

机构信息

Yusuf Hamied Department of Chemistry, Centre for Misfolding Disease, University of Cambridge, Cambridge, UK.

Center for Biomolecular Condensates, James McKelvey School of Engineering, Washington University in St. Louis, St. Louis, MO, USA.

出版信息

Nat Commun. 2025 Apr 11;16(1):3463. doi: 10.1038/s41467-025-58736-z.

DOI:10.1038/s41467-025-58736-z
PMID:40216775
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11992113/
Abstract

Biomolecular condensates form via macromolecular phase separation. Here, we report results from our characterization of synthetic condensates formed by phase separation of mixtures comprising two types of RNA molecules and the biocompatible polymer polyethylene glycol. Purine-rich RNAs are scaffolds that drive phase separation via heterotypic interactions. Conversely, pyrimidine-rich RNA molecules are adsorbents defined by weaker heterotypic interactions. They adsorb onto and wet the interfaces of coexisting phases formed by scaffolds. Lattice-based simulations reproduce the phenomenology observed in experiments and these simulations predict that scaffolds and adsorbents have different non-random orientational preferences at interfaces. Dynamics at interfaces were probed using single-molecule tracking of fluorogenic probes bound to RNA molecules. These experiments revealed dynamical anisotropy at interfaces whereby motions of probe molecules parallel to the interface are faster than motions perpendicular to the interface. Taken together, our findings have broad implications for designing synthetic condensates with tunable interfacial properties.

摘要

生物分子凝聚物通过大分子相分离形成。在此,我们报告了对由包含两种类型RNA分子和生物相容性聚合物聚乙二醇的混合物相分离形成的合成凝聚物进行表征的结果。富含嘌呤的RNA是通过异型相互作用驱动相分离的支架。相反,富含嘧啶的RNA分子是由较弱的异型相互作用定义的吸附剂。它们吸附在由支架形成的共存相的界面上并使其湿润。基于晶格的模拟重现了实验中观察到的现象学,并且这些模拟预测支架和吸附剂在界面处具有不同的非随机取向偏好。使用与RNA分子结合的荧光探针的单分子追踪来探测界面处的动力学。这些实验揭示了界面处的动力学各向异性,即探针分子平行于界面的运动比垂直于界面的运动更快。综上所述,我们的发现对设计具有可调界面性质的合成凝聚物具有广泛的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/1d9b41cabd85/41467_2025_58736_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/86bcafebb5c8/41467_2025_58736_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/cce20e5fc436/41467_2025_58736_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/ede189875213/41467_2025_58736_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/8be4112eac65/41467_2025_58736_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/1d9b41cabd85/41467_2025_58736_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/86bcafebb5c8/41467_2025_58736_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/cce20e5fc436/41467_2025_58736_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/ede189875213/41467_2025_58736_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/8be4112eac65/41467_2025_58736_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dd8/11992113/1d9b41cabd85/41467_2025_58736_Fig5_HTML.jpg

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本文引用的文献

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Reply to: The conformations of protein chains at the interface of biomolecular condensates.回复:生物分子凝聚物界面处蛋白质链的构象
Nat Commun. 2024 Nov 19;15(1):9974. doi: 10.1038/s41467-024-53576-9.
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Sequence-specific interactions determine viscoelasticity and aging dynamics of protein condensates.
凝聚物的可调亚稳性调和了它们在淀粉样纤维形成中的双重作用。
bioRxiv. 2025 Mar 22:2024.02.28.582569. doi: 10.1101/2024.02.28.582569.
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Single fluorogen imaging reveals distinct environmental and structural features of biomolecular condensates.单荧光成像揭示了生物分子凝聚物独特的环境和结构特征。
bioRxiv. 2024 Oct 7:2023.01.26.525727. doi: 10.1101/2023.01.26.525727.
序列特异性相互作用决定了蛋白质凝聚物的粘弹性和老化动力学。
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Biomolecular condensates mediate bending and scission of endosome membranes.生物分子凝聚物介导内体膜的弯曲和断裂。
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