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Synthesis of lipid membranes for artificial cells

Abstract

A major goal of synthetic biology is to understand the transition between non-living matter and life. The bottom-up development of an artificial cell would provide a minimal system with which to study the border between chemistry and biology. So far, a fully synthetic cell has remained elusive, but chemists are progressing towards this goal by reconstructing cellular subsystems. Cell boundaries, likely in the form of lipid membranes, were necessary for the emergence of life. In addition to providing a protective barrier between cellular cargo and the external environment, lipid compartments maintain homeostasis with other subsystems to regulate cellular processes. In this Review, we examine different chemical approaches to making cell-mimetic compartments. Synthetic strategies to drive membrane formation and function, including bioorthogonal ligations, dissipative self-assembly and reconstitution of biochemical pathways, are discussed. Chemical strategies aim to recreate the interactions between lipid membranes, the external environment and internal biomolecules, and will clarify our understanding of life at the interface of chemistry and biology.

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Fig. 1: Prebiotic lipid synthesis.
Fig. 2: Prebiotic self-assembly of single-chain amphiphiles.
Fig. 3: De novo formation of lipid compartments.
Fig. 4: Autocatalysis and dissipative self-assembly.
Fig. 5: Control of vesicle self-assembly, aggregation and hierarchical order.
Fig. 6: The compartmentalized central dogma of biology.
Fig. 7: Life-like phenotypes of artificial cells.

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Acknowledgements

This work was supported by US National Science Foundation grant EF-1935372. The authors thank J. R. Winnikoff for helpful manuscript edits prior to submission and image inspiration, and A. Fracassi and R. J. Brea for their critical reading of the manuscript.

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K.A.P. drafted the manuscript and figures. K.A.P. and N.K.D. discussed, wrote and edited the manuscript prior to submission.

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Correspondence to Neal K. Devaraj.

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Glossary

Protocells

Primitive, abiotic ‘original’ cells. In synthetic biology, refers to self-assembling chemical systems with life-like characteristics.

Kennedy pathway

Biochemical pathway for the de novo synthesis of phosphatidylethanolamine and phosphatidylcholine in cells; this was the first pathway elucidated for phospholipid biosynthesis.

Lands cycle

Biochemical pathway of deacylation and reacylation for the remodelling of phospholipids.

Autopoiesis

From the Greek auto ‘self’ and poiesis ‘formation’: a property of a system that enables maintenance and reproduction of itself through self-regulation.

Organelles

Specialized subcellular structures that perform specific functions for the cell.

In vitro transcription and translation

(TXTL). A cell-free system of minimal biochemical components necessary to synthesize a protein from a DNA template.

Proteoliposomes

Liposomes in which proteins have been incorporated in the membrane.

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Podolsky, K.A., Devaraj, N.K. Synthesis of lipid membranes for artificial cells. Nat Rev Chem 5, 676–694 (2021). https://doi.org/10.1038/s41570-021-00303-3

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