Cyclophospholipids Enable a Protocellular Life Cycle
Open accessAbstract
High Resolution Image Download MS PowerPoint Slide There is currently no plausible path for the emergence of a self-replicating protocell, because prevalent formulations of model protocells are built with fatty acid vesicles that cannot withstand the concentrations of Mg 2+ needed for the function and replication of nucleic acids. Although prebiotic chelates increase the survivability of fatty acid vesicles, the resulting model protocells are incapable of growth and division. Here, we show that protocells made of mixtures of cyclophospholipids and fatty acids can grow and divide in the presence of Mg 2+ -citrate. Importantly, these protocells retain encapsulated nucleic acids during growth and division, can acquire nucleotides from their surroundings, and are compatible with the nonenzymatic extension of an RNA oligonucleotide, chemistry needed for the replication of a primitive genome. Our work shows that prebiotically plausible mixtures of lipids form protocells that are active under the conditions necessary for the emergence of Darwinian evolution.
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Cites
Prebiotic Systems Chemistry: New Perspectives for the Origins of Life
Ruiz-Mirazo, K., Briones, C., & de la Escosura, A. (2014) · Chemical Reviews · doi:10.1021/cr2004844 · Cited by 930 · see citing works
The Emergence of Competition Between Model Protocells
Chen, I. A., Roberts, R. W., & Szostak, J. W. (2004) · Science · doi:10.1126/science.1100757 · Cited by 435 · see citing works
Self-citationRibozyme-catalyzed transcription of an active ribozyme
Wochner, A., Attwater, J., Coulson, A., & Holliger, P. (2011) · Science · doi:10.1126/science.1200752 · Cited by 399 · see citing works
Forsythe, J. G., Yu, S., Mamajanov, I., Grover, M. A., Krishnamurthy, R., Fernández, F. M., & Hud, N. V. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201503792 · Cited by 324 · see citing works
Self-citationProtocells and RNA Self-Replication
Joyce, G. F., & Szostak, J. W. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a034801 · Cited by 308 · see citing works
Self-citationLipid formation by aqueous Fischer-Tropsch-type synthesis over a temperature range of 100 to 400 °C
Rushdi, A. I., & Simoneit, B. R. T. (2001) · Origins of life and evolution of the biosphere · doi:10.1023/a:1006702503954 · Cited by 274 · see citing works
Boundary structures are formed by organic-components of the Murchison carbonaceous chondrite
Deamer, D. W. (1985) · Nature · doi:10.1038/317792a0 · Cited by 270 · see citing works
Amplification of RNA by an RNA polymerase ribozyme
Horning, D. P., & Joyce, G. F. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610103113 · Cited by 261 · see citing works
A kinetic study of the growth of fatty acid vesicles
Chen, I. A., & Szostak, J. W. (2004) · Biophysical Journal · doi:10.1529/biophysj.104.039875 · Cited by 251 · see citing works
Self-citationPrebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water
Foden, C. S., Islam, S., Fernández-García, C., Maugeri, L., Sheppard, T. D., & Powner, M. W. (2020) · Science · doi:10.1126/science.abd5680 · Cited by 205 · see citing works
Darwinian evolution in a translation-coupled RNA replication system within a cell-like compartment
Ichihashi, N., Usui, K., Kazuta, Y., Sunami, T., Matsuura, T., & Yomo, T. (2013) · Nature Communications · doi:10.1038/ncomms3494 · Cited by 186 · see citing works
Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth
Hardy, M. D., Yang, J., Selimkhanov, J., Cole, C. M., Tsimring, L. S., & Devaraj, N. K. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506704112 · Cited by 181 · see citing works
Dry/Wet Cycling and the Thermodynamics and Kinetics of Prebiotic Polymer Synthesis
Ross, D., & Deamer, D. (2016) · Life · doi:10.3390/life6030028 · Cited by 157 · see citing works
Ribozyme-catalysed RNA synthesis using triplet building blocks
Attwater, J., Raguram, A., Morgunov, A. S., Gianni, E., & Holliger, P. (2018) · eLife · doi:10.7554/elife.35255 · Cited by 147 · see citing works
Semipermeable lipid bilayers exhibit diastereoselectivity favoring ribose
Sacerdote, M. G., & Szostak, J. W. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408440102 · Cited by 147 · see citing works
Self-citationSpringsteen, G., Yerabolu, J. R., Nelson, J., Rhea, C. J., & Krishnamurthy, R. (2018) · Nature Communications · doi:10.1038/s41467-017-02591-0 · Cited by 132 · see citing works
Self-citationBlack, R. A., Blosser, M. C., Stottrup, B. L., Tavakley, R., Deamer, D. W., & Keller, S. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1300963110 · Cited by 123 · see citing works
Maurer, S. E., Deamer, D. W., Boncella, J. M., & Monnard, P.-A. (2009) · Astrobiology · doi:10.1089/ast.2009.0384 · Cited by 121 · see citing works
Chain-length heterogeneity allows for the assembly of fatty acid vesicles in dilute solutions
Budin, I., Prywes, N., Zhang, N., & Szostak, J. W. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2014.07.067 · Cited by 88 · see citing works
Self-citationBit by bit: The Darwinian basis of life
Joyce, G. F. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001323 · Cited by 45 · see citing works
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- Authors
- Toparlak, Ö. D., Sebastianelli, L., Egas Ortuno, V., Karki, M., Xing, Y., Szostak, J. W., Krishnamurthy, R., & Mansy, S. S.
- Affiliations
- University of Trento (IT)
- University of Alberta (CA)
- Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States
- Scripps Research Institute (US)
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Szostak, Jack W.
- Krishnamurthy, Ramanarayanan
- Mansy, Sheref S.
- ORCID
- Venue
- ACS Nano
- Publisher
- American Chemical Society (ACS)
- Published
- 2023-12-01
- Volume
- 17
- Issue
- 23
- Pages
- 23772-23783
- ISSN
- 1936-0851 (ISSN-L)
- 1936-086X
- PMC
- PMC10722605
- OpenAlex
- W4389245104
- Cited by
- 26
- References
- 20
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 10
- FWCI
- 2.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- ACS Nano (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Iris (University of Trento) (submittedVersion, cc-by-nc-nd)
- Knowledge@UChicago (University of Chicago) (submittedVersion)
- University of Chicago
- Funders
- Howard Hughes Medical Institute
- Gordon and Betty Moore Foundation (11479)
- Alfred P. Sloan Foundation (G-2022-19518)
- Horizon 2020 Framework Programme (824060)
- Natural Sciences and Engineering Research Council of Canada (RGPIN-2020-04375)
- Simons Foundation (290358FY18, 290363, 327124FY19, 290358FY19)
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- protocells, fatty acid vesicles, magnesium, nucleic acid encapsulation, nucleotide uptake, origin of life, self-replication, lipid mixtures
- MeSH terms
- Citrates, Fatty Acids, Nucleic Acids, RNA, Artificial Cells
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