한빛사논문
Sumit Kumar 1,2, Mamata Karmacharya1,3, Issac J. Michael1,2, Yongjun Choi 1,2, Junyoung Kim1,2, InUn Kim1 and Yoon-Kyoung Cho 1,2,*
1Center for Soft and Living Matter, Institute for Basic Science (IBS), Ulsan, South Korea. 2Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea. 3Department of Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea.
*Corresponding author.
Abstract
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.
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