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DNA-empowered synthetic cells as minimalistic life forms

Nature Reviews Chemistry (2024)Cite this article

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Abstract

Cells, the fundamental units of life, orchestrate intricate functions — motility, adaptation, replication, communication, and self-organization within tissues. Originating from spatiotemporally organized structures and machinery, coupled with information processing in signalling networks, cells embody the ‘sensor–processor–actuator’ paradigm. Can we glean insights from these processes to construct primitive artificial systems with life-like properties? Using de novo design approaches, what can we uncover about the evolutionary path of life? This Review discusses the strides made in crafting synthetic cells, utilizing the powerful toolbox of structural and dynamic DNA nanoscience. We describe how DNA can serve as a versatile tool for engineering entire synthetic cells or subcellular entities, and how DNA enables complex behaviour, including motility and information processing for adaptive and interactive processes. We chart future directions for DNA-empowered synthetic cells, envisioning interactive systems wherein synthetic cells communicate within communities and with living cells.

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Fig. 1: DNA as a structural component for synthetic cells based on liposomes, polymersomes, colloids and emulsions.
Fig. 2: DNA condensation to form all-DNA or DNA-rich synthetic cells.
Fig. 3: DNA to generate functional entities at the cell wall and in the lumen.
Fig. 4: Information processing in DNA synthetic cells with a metabolism for adaptive and interactive proto-ecologies.
Fig. 5: Future viewpoint on DNA nanotechnology in synthetic cell research.

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Acknowledgements

We acknowledge funding by the Deutsche Forschungsgemeinschaft in WA 3084/19-1, and the Collaborative Research Center 1551 “Polymer Concepts in Cellular Function”. A.W. acknowledges funding via a Gutenberg Research Professorship underpinning his Life-Like Materials Program. A.S. acknowledges the support from IIT Roorkee for Faculty Initiation Grant (FIG-101023) and RSC Research Fund grant (R23-1045418311). A.S. and L.B.P. acknowledge personal grants by the Alexander von Humboldt Foundation. M.M. acknowledges funding through the European Union’s Horizon 2022 research and innovation programme under the Marie Skłodowska-Curie grant agreement DNAPC4ImunoMol-101111348.

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Authors and Affiliations

  1. Life-Like Materials and Systems, Department of Chemistry, University of Mainz, Mainz, Germany

    Avik Samanta, Lorena Baranda Pellejero, Marcos Masukawa & Andreas Walther

  2. Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, India

    Avik Samanta

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A.S. and A.W. researched data for the article, contributed to the discussion of content, writing and reviewing/editing the manuscript before submission. L.B. and M.M. researched data for the article, contributed to discussion of content, and writing.

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Glossary

Aptamers

Oligonucleotides that selectively bind a target ligand (for example, lysozyme, oncogenes, ATP and dopamine) and which are usually obtained by systematic in vitro selection procedures, commonly known as SELEX (Systematic Evolution of Ligands by EXponential enrichment).

Aqueous two-phase emulsion systems

(ATPS). Spontaneous phase separation of a mixture of two polymers, a polymer and a kosmotropic salt, or two salts (one chaotropic and one kosmotropic) in water, used for the efficient separation of biomolecules.

Bottom–up approach

An approach in which (bio)chemically synthesized components are assembled rather than extracted from biological entities to obtain a synthetic cell model.

Chemical reaction networks

A set of interconnected chemical reactions that can give rise to complex behaviour (for example, oscillations), signal processing and chemical computation.

Coacervates

Water-rich droplet phase formed by associative phase segregation of at least two interacting compounds or segregative phase separation of one compound.

DNA nanostructures

Stable nanoscopic structures made exclusively from DNA using base-pairing interactions and various other structural tools of DNA nanotechnology, such as Holliday junctions, blunt-end stacking and triplex formation.

DNA origami

Two-dimensional or three-dimensional, well-defined nanostructures assembled from a long circular ssDNA scaffold and a mixture of short ssDNA staples by duplex-mediated folding.

DNAzyme

Catalytically active DNA molecules that are often used to cleave the phosphodiester bond in a RNA target molecule in the presence of certain metal ion cofactors.

Dynamic strand displacement reaction

The dynamic strand displacement (DSD) reaction is the process by which an invader strand of longer complementarity hybridizes onto a double-stranded DNA (dsDNA) with incomplete hybridization, displacing the shorter of the previously hybridized strands. These reactions are driven by the length of the non-hybridized domains in the parent dsDNA, also known as toeholds. The result is a dsDNA with a higher thermodynamic stability, typically a longer dsDNA, and a released single-stranded DNA (ssDNA) previously bound in the dsDNA.

Hybridization chain reaction

(HCR). An isothermal enzyme-free polymerization technique in which two sets of DNA hairpin molecules undergo a chain reaction in the presence of an initiator molecule containing a complementary domain of the toehold sequence of one of the hairpins and the loop of the other.

Macromolecular crowding

Molecular crowding can occur in concentrated solutions of polymers and colloids to accelerate catalysis or induce self-assembly (for example, by depletion interactions) via nonspecific interactions.

Nanopores

Channels that enable the transport of ions, small molecules or large macromolecules (for example, proteins) through lipid bilayer membranes, usually consisting of proteins or self-assembled macromolecules, such as DNA.

Synthetic cells

Engineered microcompartments that aim to mimic aspects of the architecture, functions or behaviours of living cells.

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Samanta, A., Baranda Pellejero, L., Masukawa, M. et al. DNA-empowered synthetic cells as minimalistic life forms. Nat Rev Chem (2024). https://doi.org/10.1038/s41570-024-00606-1

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