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  • Review Article
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Hydrogels as functional components in artificial cell systems

Abstract

Recent years have seen substantial efforts aimed at constructing artificial cells from various molecular components with the aim of mimicking the processes, behaviours and architectures found in biological systems. Artificial cell development ultimately aims to produce model constructs that progress our understanding of biology, as well as forming the basis for functional bio-inspired devices that can be used in fields such as therapeutic delivery, biosensing, cell therapy and bioremediation. Typically, artificial cells rely on a bilayer membrane chassis and have fluid aqueous interiors to mimic biological cells. However, a desire to more accurately replicate the gel-like properties of intracellular and extracellular biological environments has driven increasing efforts to build cell mimics based on hydrogels. This has enabled researchers to exploit some of the unique functional properties of hydrogels that have seen them deployed in fields such as tissue engineering, biomaterials and drug delivery. In this Review, we explore how hydrogels can be leveraged in the context of artificial cell development. We also discuss how hydrogels can potentially be incorporated within the next generation of artificial cells to engineer improved biological mimics and functional microsystems.

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Fig. 1: Approaches to the creation of artificial cells and the important functionalities of artificial cell systems.
Fig. 2: Chemical structures of the repeat units or primary sequences of common polymers used within hydrogel formation.
Fig. 3: Eukaryotic cell features that can be mimicked by hydrogels.
Fig. 4: The wide variety of architectures hydrogel systems have been able to form.
Fig. 5: Compartmentalization within hydrogel artificial cell systems.
Fig. 6: Hydrogels as communication tools and regulatory systems.
Fig. 7: Potential future hydrogel-inspired artificial cell structures with appropriate functionalities indicated.

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Acknowledgements

This work was supported by a UK Research and Innovation (UKRI) Future Leaders Fellowship, grant reference number MR/S031537/1 (awarded to Y.E.); an Engineering and Physical Sciences Research Council (EPSRC) Centre for Doctoral Training Studentship from the Institute of Chemical Biology, grant reference number EP/S023518 (awarded to M.E.A.), an EPSRC Doctoral Prize Fellowship (awarded to J.W.H.) and an EPSRC grant, reference number EP/V048651/1.

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M.E.A., J.W.H. and Y.E. proposed the framework of this Review. All authors contributed through researching, writing and editing the Review.

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Glossary

Artificial cell

An engineered device that attempts to mimic the form, function and/or behaviours of biological cells.

Synthetic biology

A field that involves the redesign of existing organisms (top down) or the construction of new cell-like entities from molecular building blocks (bottom up).

Vesicle

Aqueous compartment coated with a bilayer of amphiphilic molecules (usually lipids).

Coacervates

A colloid rich aqueous phase that is formed through liquid–liquid phase separation.

Nanogel

A nanoparticle (nanometre size) that comprises a hydrogel network.

Microgel

A microparticle (micrometre size) that comprises a hydrogel network.

Droplet interface bilayer

(DIB). A lipid bilayer that is formed between aqueous droplets in oil from the contact of water–oil interfaces in the presence of a suitable phospholipid.

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Allen, M.E., Hindley, J.W., Baxani, D.K. et al. Hydrogels as functional components in artificial cell systems. Nat Rev Chem 6, 562–578 (2022). https://doi.org/10.1038/s41570-022-00404-7

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