Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth
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Significance: We report on the design and synthesis of an artificial cell membrane that sustains continual growth. Lipid membranes are ubiquitous in all domains of life. Numerous studies have exploited the ability of lipids to self-assemble into bilayer vesicles with properties reminiscent of cellular membranes, but previous work has yet to mimic nature’s ability to support persistent phospholipid membrane formation. In this work, we have developed an artificial cell membrane that continually synthesizes all of the components needed to form additional catalytic membranes. These results demonstrate that complex lipid membranes capable of indefinite self-synthesis can emerge when supplied with simpler chemical building blocks.
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A model lipid catalyst with a Cu1+-chelating headgroup and three modified fatty acid chains catalysed covalent bond formation between an alkyne-derivatized lysophospholipid and an azide-derivatized fatty acid analogue, forming a two-chain phospholipid analogue.
“The model lipid catalyst has a headgroup constituting a hydrophilic chelator for Cu1+ ions and the hydrophobic moieties were three modified fatty acid chains. This amphiphilic molecule served as effective catalyst for the covalent bond formation between an alkyne-derivatized lysophospholipid and an azide-derivatized fatty acid analogue, leading to the formation of two-chain phospholipid analogue.”
From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [193]
The lipid-embodied network in Devaraj's experiment has four food compounds, three of which generate a lipid catalyst in two consecutive reactions.
“The lipid-embodied network has four food compounds, three of which generate a lipid catalyst in two consecutive reactions.”
From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [193]
The experimental results of Devaraj on lipid-catalysed lipid modification are describable by a simple mutually catalytic network in line with the Kauffman-Hordijk model, as well as by the formalisms of M-GARD.
“The experimental results provided are describable by a simple mutually catalytic network in line with the Kauffman–Hordijk model, as well as by the formalisms of M-GARD (previous section).”
From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [193]
The catalyst enhances the rate of its own formation, as well as that of a reaction generating a two-chain phospholipid from a single chain phospholipid and a fatty acid analogue.
“The catalyst then enhances the rate of its own formation, as well as that of a reaction generating a two-chain phospholipid from a single chain phospholipid and a fatty acid analogue.”
From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [193]
There is a first published experimental instance of a simple lipid-based GARD network.
“but highlight a first published experimental instance of a simple lipid-based GARD network [193].”
From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [193]
There are insurmountable hurdles for comprehensive experimental verification of the model.
“Regarding evidence for our model's validity, we point out the insurmountable hurdles for comprehensive experimental verification, but highlight a first published experimental instance of a simple lipid-based GARD network [193].”
From Systems protobiology: origin of life in lipid catalytic networks (2018) · cites this paper as [193]
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Self-citation
- Authors
- Hardy, M. D., Yang, J., Selimkhanov, J., Cole, C. M., Tsimring, L. S., & Devaraj, N. K.
- Affiliations
- University of California San Diego (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-06-22
- Volume
- 112
- Issue
- 27
- Pages
- 8187-8192
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4500204
- OpenAlex
- W1952600287
- Cited by
- 181
- References
- 52
- Citations by year
- 2026: 15 · 2025: 13 · 2024: 13 · 2023: 17 · 2022: 12 · 2021: 17 · 2020: 20 · 2019: 26 · 2018: 16 · 2017: 20 · 2016: 6 · 2015: 6
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense (W911NF-13-1-0383)
- National Science Foundation (CHE-1254611)
- HHS | National Institutes of Health (P50GM085764)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Keywords
- autocatalysis, phospholipid synthesis, model membranes, membrane growth, vesicle growth, membrane remodeling, biomimetic membranes, lipid bilayer formation, origin of life
- MeSH terms
- Catalysis, Cell Membrane, Copper, Lipid Bilayers, Membrane Lipids, Membranes, Artificial, Models, Chemical, Magnetic Resonance Spectroscopy, Phosphatidylcholines, Phospholipids, Triazoles, Molecular Structure, Microscopy, Confocal, Microscopy, Electron, Transmission, Unilamellar Liposomes, Time-Lapse Imaging, Cycloaddition Reaction
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