An Enzyme‐Coated Metal–Organic Framework Shell for Synthetically Adaptive Cell Survival

Abstract

Abioactive synthetic porous shell was engineered to enable cells to survive in an oligotrophic environment. Eukaryotic cells (yeast) were firstly coated with a b-galactosidase (b-gal), before crystallization of ametal-organic framework (MOF) film on the enzyme coating;t hereby producing ab ioactive porous synthetic shell. The b-gal was an essential component of the bioactive shell as it generated nutrients (that is,glucose and galactose) required for cell viability in nutrientdeficient media (lactose-based). Additionally,the porous MOF coating carried out other vital functions,s uch as 1) shielding the cells from cytotoxic compounds and radiation, 2) protecting the non-native enzymes (b-gal in this instance) from degradation and internalization, and 3) allowing for the diffusion of molecules essential for the survival of the cells. Indeed, this bioactive porous shell enabled the survival of cells in simulated extreme oligotrophic environments for more than 7days, leading to ad ecrease in cell viability less than 30 %, versus a9 9% decrease for naked yeast. When returned to optimal growth conditions the bioactive porous exoskeleton could be removed and the cells regained full growth immediately.T he construction of bioactive coatings represents ac onceptually new and promising approach for the next-generation of cell-based researchand application, and is an alternative to synthetic biology or genetic modification.

Therapeutic Potential of Biomineralization‐Based Engineering

“…[24] MnO 2 nanoparticles with enzyme-like properties have been deposited on yeast cells as functional shells, which provide switchable protection in response to glutathione (GSH) stimulus. [103] The bioinspired mineralization presents multiplex cytoprotection for individual living cells. [102] Metal-organic frameworks (MOFs) that are thermally and chemically robust can be incorporated into a single cell as a mineralized shell, providing a protective layer with permeable pores for transporting essential nutrients.…”

Manganese Dioxide Nanozymes as Responsive Cytoprotective Shells for Individual Living Cell Encapsulation

“…Owing to the preservation of cell viability and functionality in harsh environments,the single cell encapsulation technique has exhibited its potential in am ultiplicity of fields,s uch as biocatalysis,cell-based sensors,and therapy. [1][2][3][4] Va rious coating shells including silica (SiO 2 ), [5,6] calcium phosphates (CaP), [7] polymers, [8][9][10] as well as metal coordination complexes [11,12] have been widely exploited to shield cells from hostile stressors and external environments.D espite the potential advantages of above protective coatings,t he practical utilization of these shells in real systems still remains problematic.F irstly,t hese coatings usually provide limited protection against molecular toxic chemicals,s uch as H 2 O 2 , owing to their intrinsic inertness and permeability.A fter rapidly equilibrating across the shells,t oxic chemicals can ultimately induce the death of cells. [13][14][15] Secondly,t hese coating shells can only be decomposed by treatment with some harmful compounds,including HCl and EDTA, indicating the further impossibility of non-invasive control of cell functions and single cell based biology.…”

Nanoarchitectonics of Biofunctionalized Metal–Organic Frameworks with Biological Macromolecules and Living Cells

“…Such modular approaches of MOF growth under biological conditions facilitate the tuning of pores, chemical functionality, and size of the resulting composite. A proof‐of‐concept is that living eukaryotic cells when containing an MOF‐shield with externally originating enzymes were capable of transforming disaccharides into monosaccharides . The Saccharomyces cerevisiae (baker's yeast) cells are devoid of lactose and require genetic engineering to construct S .…”

“…An illustration showing the incorporation and removal of the bioactive porous (β‐gal/ZIF‐8) protective layer for synthetically adaptive living cell survival. Reproduced with permission . Copyright 2017, WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.…”

“…A proofofconcept is that living eukaryotic cells when containing an MOFshield with externally originating enzymes were capable of transforming disaccharides into monosaccha rides. [85] The Saccharomyces cerevisiae (baker's yeast) cells are devoid of lactose and require genetic engineering to construct S. cerevisiae strains for lactose consumption. The S. cerevisiae coated with βgalactosidase (βgal) which was further coated with a ZIF8 shell exhibited improved cell survival in a medium without nutrient (Figure 10).…”