Enzyme-mediated nitric oxide production in vasoactive erythrocyte membrane-enclosed coacervate protocells

Songyang Liu, Yanwen Zhang, Mei Li, Li Xiong, Zijian Zhang, Xiaohai Yang, Xiaoxiao He, Kemin Wang, Jianbo Liu*, Stephen Mann*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

45 Citations (Scopus)
125 Downloads (Pure)

Abstract

The design and construction of synthetic therapeutic protocells capable of establishing cognate chemical communication channels with living cells is an important challenge for synthetic biology and bio-engineering. Here we develop a step towards protocell-mediated nitric-oxide-induced vasodilation by constructing a new synthetic cell model based on bio-derived coacervate vesicles with high haemocompatibility and increased blood circulation times. The hybrid protocells are prepared by the spontaneous self-assembly of haemoglobin-containing erythrocyte membrane fragments on the surface of preformed polysaccharide–polynucleotide coacervate micro-droplets containing glucose oxidase. We use the sequestered enzymes to program a spatially coupled glucose oxidase/haemoglobin reaction cascade, which in the presence of glucose and hydroxyurea generates a protocell-mediated flux of nitric oxide that we exploit for in vitro and in vivo blood vessel vasodilation. Taken together, our results provide new opportunities for the development of endogenously organized cell-like entities (biocompatible micro-bots) geared specifically towards active interfacing with individual living cells and cell communities.
Original languageEnglish
Pages (from-to)1165–1173
Number of pages14
JournalNature Chemistry
Volume12
Early online date20 Nov 2020
DOIs
Publication statusPublished - 1 Dec 2020

Structured keywords

  • Bristol BioDesign Institute
  • Max Planck Bristol

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