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

Nature Chemistry
Songyang LiuStephen Mann

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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Citations

Jan 6, 2021·Nanoscale Horizons : the Home for Rapid Reports of Exceptional Significance in Nanoscience and Nanotechnolgy·Yibo LiuJuewen Liu
Feb 11, 2021·Journal of the American Chemical Society·Yanwen ZhangStephen Mann
May 6, 2021·Chemical Communications : Chem Comm·Yufeng ChenJianbo Liu
Jul 24, 2021·Biomaterials·David William GreenArtemis Stamboulis
Jul 22, 2021·Chemical Communications : Chem Comm·Dishi WangDietmar Appelhans
Nov 3, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Wakana SatoKatarzyna P Adamala
Nov 26, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Yanwen ZhangJianbo Liu

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Methods Mentioned

BETA
fluorescence microscopy
electrophoresis
confocal microscopy
fluorescence-activated cell sorting
FACS
fluorescence imaging
Fluorescence
tension

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