Phase-separated bienzyme compartmentalization as artificial intracellular membraneless organelles for cell repair  

作　　者：Yanwen Zhang Shixin Wang Yuling Yan Xiaoxiao He Zefeng Wang Shaohong Zhou Xiaohai Yang Kemin Wang Jianbo Liu 

机构地区：[1]State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Chemistry and Chemical Engineering,Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province,Hunan University,Changsha 410082,China

出　　处：《Science China Chemistry》2023年第3期845-852,共8页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(21735002,22177032,32101082);the Science Fund for Distinguished Young Scholars of Hunan Province(2021JJ10013);the Hunan Province Innovative Talent Funding for Postdoctoral Fellows(2021RC2059);the Postdoctoral Science Foundation of China(2021TQ0103,2021M690957).

摘　　要：Implanting artificial organelles in living cells is capable of correcting cellular dysfunctionalities for cell repair and biomedical applications. In this work, phase-separated bienzyme-loaded coacervate microdroplets are established as a model of artificial membraneless organelles in endothelial dysfunctional cells for the cascade enzymatic production of nitric oxide(NO) with a purpose of correcting cellular NO deficiency. We prepared the coacervate microdroplets via liquid-liquid phase separation of oppositely charged polyelectrolytes, in which glucose oxidase/horseradish peroxidase-mediated cascade reaction was compartmented. After the coacervate microdroplets were implanted in NO-deficient dysfunctional cells, the compartments maintained a phase-separated liquid droplet structure, which facilitated a significant enhancement of NO production in the dysfunctional cells. The recovery of NO production was further exploited to inhibit clot formation in blood plasma located in the cell suspension. This demonstrated a proof-of-concept design of artificial organelles in dysfunctional cells for cell repair and anticoagulation-related medical applications. Our results demonstrate an approach for the construction of coacervate droplets through phase separation for the generation of artificial membraneless organelles, which can be designed to provide an array of functionalities in living organisms that have the potential to be used in the field of cell engineering and medical therapy.

关 键 词：artificial membraneless organelles coacervate microdroplets nitric oxide liquid-liquid phase separation cell repair 

分 类 号：Q813[生物学—生物工程]