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酶模拟促进人工细胞向哺乳动物细胞的信号转导。

Enzyme Mimic Facilitated Artificial Cell to Mammalian Cell Signal Transfer.

机构信息

Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav Wieds Vej 14, 8000, Aarhus, Denmark.

出版信息

Angew Chem Int Ed Engl. 2021 Aug 16;60(34):18704-18711. doi: 10.1002/anie.202104904. Epub 2021 Jul 16.

Abstract

Catalyzing biochemical reactions with enzymes and communicating with neighboring cells via chemical signaling are two fundamental cellular features that play a critical role in maintaining the homeostasis of organisms. Herein, we present an artificial enzyme (AE) facilitated signal transfer between artificial cells (ACs) and mammalian HepG2 cells. We synthesize metalloporphyrins (MPs) based AEs that mimic cytochrome P450 enzymes (CYPs) to catalyze a dealkylation and a hydroxylation reaction, exemplified by the conversion of resorufin ethyl ether (REE) to resorufin and coumarin (COU) to 7-hydroxycoumarin (7-HC), respectively. The AEs are immobilized in hydrogels to produce ACs that generate the two diffusive fluorophores, which can diffuse into HepG2 cells and result in dual intracellular emissions. This work highlights the use of AEs to promote AC to mammalian signal transfer, which opens up new opportunities for integrating the synthetic and living world with a bottom-up strategy.

摘要

用酶催化生化反应和通过化学信号与邻近细胞进行通信是两种基本的细胞特征,它们在维持生物体的内稳态方面起着至关重要的作用。在此,我们提出了一种人工酶(AE)促进人工细胞(AC)与哺乳动物 HepG2 细胞之间的信号传递。我们合成了基于金属卟啉(MPs)的 AE,模拟细胞色素 P450 酶(CYPs)催化去烷基化和羟化反应,分别以将色原酮乙基醚(REE)转化为色原酮和香豆素(COU)转化为 7-羟基香豆素(7-HC)为例。AE 被固定在水凝胶中以产生 AC,产生两种扩散荧光团,它们可以扩散到 HepG2 细胞中,并导致双细胞内发射。这项工作强调了使用 AE 促进 AC 与哺乳动物的信号传递,这为使用自下而上的策略整合合成和生命世界开辟了新的机会。

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