2. Academic Validation
  3. Enzyme-mediated nitric oxide production in vasoactive erythrocyte membrane-enclosed coacervate protocells

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

  • Nat Chem. 2020 Dec;12(12):1165-1173. doi: 10.1038/s41557-020-00585-y.
Songyang Liu 1,  Yanwen Zhang 1,  Mei Li 2,  Li Xiong 3,  Zijian Zhang 3,  Xiaohai Yang 1,  Xiaoxiao He 1,  Kemin Wang 1,  Jianbo Liu 4 5,  Stephen Mann 6 7
Affiliations

Affiliations

  • 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, P. R. China.
  • 2 Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol, UK.
  • 3 The Second Xiangya Hospital, Central South University, Changsha, P. R. China.
  • 4 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, P. R. China. liujianbo@hnu.edu.cn.
  • 5 Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol, UK. liujianbo@hnu.edu.cn.
  • 6 Centre for Protolife Research, School of Chemistry, University of Bristol, Bristol, UK. s.mann@bristol.ac.uk.
  • 7 Max Planck-Bristol Centre for Minimal Biology, University of Bristol, Bristol, UK. s.mann@bristol.ac.uk.
PMID: 33219364 DOI: 10.1038/s41557-020-00585-y
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.

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