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Programmed exosome fusion for energy generation in living cells
Nature Catalysis ( IF 37.8 ) Pub Date : 2021-09-13 , DOI: 10.1038/s41929-021-00669-z
Sumit Kumar 1, 2 , Mamata Karmacharya 1, 3 , Issac J. Michael 1, 2 , Yongjun Choi 1, 2 , Junyoung Kim 1, 2 , InUn Kim 1 , Yoon-Kyoung Cho 1, 2
Affiliation  

Biological membrane-enclosed organelles are fascinating examples of spatially confined nanoreactors for biocatalytic transformations such as cascade reactions involving multiple enzymes; however, the fabrication of their synthetic mimics remains a considerable challenge. Here we demonstrate supramolecular chemistry-based bridging of two membranes leading to controlled fusion of exosomes that act as nanoreactors for effective biocatalytic cascades, with prolonged functionality inside of living cells. Exosome membrane proteins were chemically engineered with a catechol moiety to drive fusion by supramolecular complexation to bridge the membranes. This strategy successfully encapsulated multiple enzymes and assembled the minimal electron transport chain in the plasma membrane, leading to tuneable, enhanced catalytic cascade activity capable of ATP synthesis inside of tissue spheroids. This nanoreactor was functional for many hours after uptake into living cells, showed successful penetration into tissue spheroids and repaired the damaged region by supplying ATP, all of which represent an advance in the mimicking of nature’s own organelles.



中文翻译:

用于在活细胞中产生能量的程序性外泌体融合

生物膜封闭的细胞器是空间受限的纳米反应器的迷人例子,用于生物催化转化,例如涉及多种酶的级联反应;然而,制造它们的合成模拟物仍然是一个相当大的挑战。在这里,我们展示了基于超分子化学的两个膜的桥接,导致外泌体的受控融合,这些外泌体充当有效生物催化级联的纳米反应器,在活细胞内具有延长的功能。外泌体膜蛋白用儿茶酚部分化学工程化,通过超分子络合驱动融合以桥接膜。该策略成功封装了多种酶,并在质膜中组装了最小的电子传输链,从而实现了可调谐、增强的催化级联活性能够在组织球体内合成 ATP。这种纳米反应器在被活细胞吸收后可运行数小时,显示成功渗透到组织球体并通过提供 ATP 修复受损区域,所有这些都代表了模拟自然界自身细胞器的进步。

更新日期:2021-09-13
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