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  • Perspective
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Self-reproducing catalytic micelles as nanoscopic protocell precursors

Abstract

Protocells at life’s origin are often conceived as bilayer-enclosed precursors of life, whose self-reproduction rests on the early advent of replicating catalytic biopolymers. This Perspective describes an alternative scenario, wherein reproducing nanoscopic lipid micelles with catalytic capabilities were forerunners of biopolymer-containing protocells. This postulate gains considerable support from experiments describing micellar catalysis and autocatalytic proliferation, and, more recently, from reports on cross-catalysis in mixed micelles that lead to life-like steady-state dynamics. Such results, along with evidence for micellar prebiotic compatibility, synergize with predictions of our chemically stringent computer-simulated model, illustrating how mutually catalytic lipid networks may enable micellar compositional reproduction that could underlie primal selection and evolution. Finally, we highlight studies on how endogenously catalysed lipid modifications could guide further protocellular complexification, including micelle to vesicle transition and monomer to biopolymer progression. These portrayals substantiate the possibility that protocellular evolution could have been seeded by pre-RNA lipid assemblies.

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Fig. 1: Dynamics of micellar proliferation.
Fig. 2: Advantages of micellar systems for priming early life.
Fig. 3: Representative cases of micellar catalysis.
Fig. 4: Selection in heterogeneous catalytic micelles.
Fig. 5: Micellar reproduction and evolution.

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References

  1. Szostak, J. W., Bartel, D. P. & Luisi, P. L. Synthesizing life. Nature 409, 387–390 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Adamala, K. & Szostak, J. W. Competition between model protocells driven by an encapsulated catalyst. Nat. Chem. 5, 495–501 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lancet, D., Zidovetzki, R. & Markovitch, O. Systems protobiology: origin of life in lipid catalytic networks. J. R. Soc. Interface 15, 20180159 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Ameta, S., Matsubara, Y. J., Chakraborty, N., Krishna, S. & Thutupalli, S. Self-reproduction and Darwinian evolution in autocatalytic chemical reaction systems. Life 11, 308 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lopez, A. & Fiore, M. Investigating prebiotic protocells for a comprehensive understanding of the origins of life: a prebiotic systems chemistry perspective. Life 9, 49 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  6. Mansy, S. S. et al. Template-directed synthesis of a genetic polymer in a model protocell. Nature 454, 122–125 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kauffman, S. A. Autocatalytic sets of proteins. J. Theor. Biol. 119, 1–24 (1986).

    Article  CAS  PubMed  Google Scholar 

  8. Hordijk, W., Shichor, S. & Ashkenasy, G. The influence of modularity, seeding, and product inhibition on peptide autocatalytic network dynamics. ChemPhysChem 19, 2437–2444 (2018).

    Article  CAS  PubMed  Google Scholar 

  9. Xavier, J. C., Hordijk, W., Kauffman, S., Steel, M. & Martin, W. F. Autocatalytic chemical networks at the origin of metabolism. Proc. Biol. Sci. 287, 20192377 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wołos, A. et al. Synthetic connectivity, emergence, and self-regeneration in the network of prebiotic chemistry. Science 369, eaaw1955 (2020).

    Article  PubMed  CAS  Google Scholar 

  11. Peng, Z., Plum, A. M., Gagrani, P. & Baum, D. A. An ecological framework for the analysis of prebiotic chemical reaction networks. J. Theor. Biol. 507, 110451 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Serra, R. & Villani, M. Sustainable growth and synchronization in protocell models. Life 9, 68 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  13. Deacon, T. W. Reciprocal linkage between self-organizing processes is sufficient for self-reproduction and evolvability. Biol. Theory 1, 136–149 (2006).

    Article  Google Scholar 

  14. Adamala, K. P., Engelhart, A. E. & Szostak, J. W. Collaboration between primitive cell membranes and soluble catalysts. Nat. Commun. 7, 11041 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Matsuo, M. et al. Environment-sensitive intelligent self-reproducing artificial cell with a modification-active lipo-deoxyribozyme. Micromachines 11, 606 (2020).

    Article  PubMed Central  Google Scholar 

  16. Rajamani, S. et al. Lipid-assisted synthesis of RNA-like polymers from mononucleotides. Orig. Life Evol. Biosph. 38, 57–74 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Kurihara, K. et al. Self-reproduction of supramolecular giant vesicles combined with the amplification of encapsulated DNA. Nat. Chem. 3, 775–781 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. Segrè, D., Ben-Eli, D. & Lancet, D. Compositional genomes: prebiotic information transfer in mutually catalytic noncovalent assemblies. Proc. Natl Acad. Sci. USA 97, 4112–4117 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lancet, D., Segrè, D. & Kahana, A. Twenty years of “lipid world”: a fertile partnership with David Deamer. Life 9, 77 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  20. Sarkar, S. et al. Prebiological membranes and their role in the emergence of early cellular life. J. Membr. Biol. 253, 589–608 (2020).

    Article  CAS  PubMed  Google Scholar 

  21. Jordan, S. F. et al. Promotion of protocell self-assembly from mixed amphiphiles at the origin of life. Nat. Ecol. Evol. 3, 1705–1714 (2019).

    Article  PubMed  Google Scholar 

  22. Zhang, S. Lipid-like self-assembling peptides. Acc. Chem. Res. 45, 2142–2150 (2012).

    Article  CAS  PubMed  Google Scholar 

  23. Segrè, D., Ben-Eli, D., Deamer, D. W. & Lancet, D. The lipid world. Orig. Life Evol. Biosph. 31, 119–145 (2001).

    Article  PubMed  Google Scholar 

  24. Guttenberg, N., Virgo, N., Chandru, K., Scharf, C. & Mamajanov, I. Bulk measurements of messy chemistries are needed for a theory of the origins of life. Phil. Trans. R. Soc. A 375, 20160347 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Deamer, D. W. Boundary structures are formed by organic components of the Murchison carbonaceous chondrite. Nature 317, 792–794 (1985).

    Article  CAS  Google Scholar 

  26. Deamer, D. W. & Pashley, R. Amphiphilic components of the Murchison carbonaceous chondrite: surface properties and membrane formation. Orig. Life Evol. Biosph. 19, 21–38 (1989).

    Article  CAS  PubMed  Google Scholar 

  27. Kahana, A., Schmitt-Kopplin, P. & Lancet, D. Enceladus: first observed primordial soup could arbitrate origin-of-life debate. Astrobiology 19, 1263–1278 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Deamer, D. The role of lipid membranes in life’s origin. Life 7, 5 (2017).

    Article  CAS  PubMed Central  Google Scholar 

  29. Israelachvili, J. in Intermolecular and Surface Forces (Academic, 1992).

  30. Sakai, T., Miyaki, M., Tajima, H. & Shimizu, M. Precipitate deposition around CMC and vesicle-to-micelle transition of monopotassium monododecyl phosphate in water. J. Phys. Chem. B 116, 11225–11233 (2012).

    Article  CAS  PubMed  Google Scholar 

  31. Deamer, D. & Damer, B. Can life begin on Enceladus? A perspective from hydrothermal chemistry. Astrobiology 17, 834–839 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Namani, T., Ishikawa, T., Morigaki, K. & Walde, P. Vesicles from docosahexaenoic acid. Colloids Surf. B 54, 118–123 (2007).

    Article  CAS  Google Scholar 

  33. Zana, R. in Dynamics of Surfactant Self-Assemblies: Micelles, Microemulsions, Vesicles and Lyotropic Phases (ed. Zana, R.) 75–160 (CRC, 2005).

  34. Sammalkorpi, M., Karttunen, M. & Haataja, M. Micelle fission through surface instability and formation of an interdigitating stalk. J. Am. Chem. Soc. 130, 17977–17980 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Taylor, J., Eghtesadi, S., Points, L., Liu, T. & Cronin, L. Autonomous model protocell division driven by molecular replication. Nat. Commun. 8, 237 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Bradley, W. L. in Debating Design: From Darwin to DNA (eds Dembski, W. & Ruse, M.) 331–351 (Cambridge Univ. Press, 2004).

  37. Dwars, T., Paetzold, E. & Oehme, G. Reactions in micellar systems. Angew. Chem. Int. Ed. 44, 7174–7199 (2005).

    Article  CAS  Google Scholar 

  38. Hardy, M. D. et al. Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth. Proc. Natl Acad. Sci. USA 112, 8187–8192 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ren, C., Solís-Muñana, P., Warr, G. G. & Chen, J. L.-Y. Dynamic and modular formation of a synergistic transphosphorylation catalyst. ACS Catal. 10, 8395–8401 (2020).

    Article  CAS  Google Scholar 

  40. Fendler, J. H. & Fendler, E. J. in Catalysis in Micellar and Macromolecular Systems (Academic, 1975).

  41. La Sorella, G., Strukul, G. & Scarso, A. Recent advances in catalysis in micellar media. Green Chem. 17, 644–683 (2015).

    Article  CAS  Google Scholar 

  42. Serrano-Luginbühl, S., Ruiz-Mirazo, K., Ostaszewski, R., Gallou, F. & Walde, P. Soft and dispersed interface-rich aqueous systems that promote and guide chemical reactions. Nat. Rev. Chem. 2, 306–327 (2018).

    Article  CAS  Google Scholar 

  43. Grochmal, A., Prout, L., Makin-Taylor, R., Prohens, R. & Tomas, S. Modulation of reactivity in the cavity of liposomes promotes the formation of peptide bonds. J. Am. Chem. Soc. 137, 12269–12275 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. Stano, P. & Luisi, P. L. in Advances in Planar Lipid Bilayers and Liposomes Vol. 7 (ed. Leitmannova Liu, A.) 221–263 (Academic, 2008).

  45. Monnard, P.-A. Catalysis in abiotic structured media: an approach to selective synthesis of biopolymers. Cell. Mol. Life Sci. 62, 520–534 (2005).

    Article  CAS  PubMed  Google Scholar 

  46. Yeung, D. K. J. et al. Organocatalytic 1,3-dipolar cycloaddition reactions of ketones and azides with water as a solvent. Green Chem. 15, 2384–2388 (2013).

    Article  CAS  Google Scholar 

  47. Soares, B. et al. Chiral organocatalysts based on lipopeptide micelles for aldol reactions in water. Phys. Chem. Chem. 19, 1181–1189 (2017).

    Article  CAS  Google Scholar 

  48. Zhang, J., Meng, X.-G., Zeng, X.-C. & Yu, X.-Q. Metallomicellar supramolecular systems and their applications in catalytic reactions. Coord. Chem. Rev. 253, 2166–2177 (2009).

    Article  CAS  Google Scholar 

  49. Smith, J. D. et al. Micelle-enabled clean and selective sulfonylation of polyfluoroarenes in water under mild conditions. Green Chem. 20, 1784–1790 (2018).

    Article  CAS  Google Scholar 

  50. Otto, S., Engberts, J. B. & Kwak, J. C. Million-fold acceleration of a Diels–Alder reaction due to combined Lewis acid and micellar catalysis in water. J. Am. Chem. Soc. 120, 9517–9525 (1998).

    Article  CAS  Google Scholar 

  51. Kahana, A., Maslov, S. & Lancet, D. Dynamic lipid aptamers: non-polymeric chemical path to early life. Chem. Soc. Rev. https://doi.org/10.1039/d1cs00633a (2021).

  52. Ihara, Y., Nango, M., Kimura, Y. & Kuroki, N. Multifunctional micellar catalysis as a model of enzyme action. J. Am. Chem. Soc. 105, 1252–1255 (1983).

    Article  CAS  Google Scholar 

  53. Bukhryakov, K. V., Almahdali, S. & Rodionov, V. O. Amplification of chirality through self-replication of micellar aggregates in water. Langmuir 31, 2931–2935 (2015).

    Article  CAS  PubMed  Google Scholar 

  54. Kunishima, M., Kikuchi, K., Kawai, Y. & Hioki, K. Substrate-selective dehydrocondensation at the interface of micelles and emulsions of common surfactants. Angew. Chem. Int. Ed. 51, 2080–2083 (2012).

    Article  CAS  Google Scholar 

  55. Kellermann, M. et al. The first account of a structurally persistent micelle. Angew. Chem. Int. Ed. 43, 2959–2962 (2004).

    Article  CAS  Google Scholar 

  56. Bachmann, P. A., Luisi, P. L. & Lang, J. Autocatalytic self-replicating micelles as models for prebiotic structures. Nature 357, 57–59 (1992).

    Article  CAS  Google Scholar 

  57. Ortega-Arroyo, J., Bissette, A. J., Kukura, P. & Fletcher, S. P. Visualization of the spontaneous emergence of a complex, dynamic, and autocatalytic system. Proc. Natl Acad. Sci. USA 113, 11122–11126 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Post, E. A. & Fletcher, S. P. Controlling the kinetics of self-reproducing micelles by catalyst compartmentalization in a biphasic system. J. Org. Chem. 84, 2741–2755 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Lebedeva, M. A., Palmieri, E., Kukura, P. & Fletcher, S. P. Emergence and rearrangement of dynamic supramolecular aggregates visualized by interferometric scattering microscopy. ACS Nano 14, 11160–11168 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Sarkar, S., Dagar, S., Verma, A. & Rajamani, S. Compositional heterogeneity confers selective advantage to model protocellular membranes during the origins of cellular life. Sci. Rep. 10, 4483 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Colomer, I., Borissov, A. & Fletcher, S. P. Selection from a pool of self-assembling lipid replicators. Nat. Commun. 11, 176 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Post, E. A. & Fletcher, S. P. Dissipative self-assembly, competition and inhibition in a self-reproducing protocell model. Chem. Sci. 11, 9434–9442 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Liu, L. et al. Enzyme-free synthesis of natural phospholipids in water. Nat. Chem. 12, 1029–1034 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lojewska, Z. & Loew, L.M. Insertion of amphiphilic molecules into membranes is catalyzed by a high molecular weight non-ionic surfactant. Biochim. Biophys. Acta 899, 104–112 (1987).

    Article  CAS  PubMed  Google Scholar 

  65. Budin, I., Prywes, N., Zhang, N. & Szostak, J. W. Chain-length heterogeneity allows for the assembly of fatty acid vesicles in dilute solutions. Biophys. J. 107, 1582–1590 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wamberg, M. C. et al. Synthesis of lipophilic guanine N-9 derivatives: membrane anchoring of nucleobases tailored to fatty acid vesicles. Bioconjugate Chem. 28, 1893–1905 (2017).

    Article  CAS  Google Scholar 

  67. Bell, T. N., Feng, K., Calvin, G., Van Winkle, D. H. & Lenhert, S. Organic composomes as supramolecular aptamers. ACS Omega 5, 27393–27400 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Okamoto, Y., Kishi, Y., Ishigami, T., Suga, K. & Umakoshi, H. Chiral selective adsorption of ibuprofen on a liposome membrane. J. Phys. Chem. B 120, 2790–2795 (2016).

    Article  CAS  PubMed  Google Scholar 

  69. Pereira de Souza, T. et al. New insights into the growth and transformation of vesicles: a free-flow electrophoresis study. J. Phys. Chem. B 119, 12212–12223 (2015).

    Article  CAS  PubMed  Google Scholar 

  70. Toparlak, Ö. D., Wang, A. & Mansy, S. Population-level membrane diversity triggers growth and division of protocells. JACS Au 1, 560–568 (2020).

    Article  CAS  Google Scholar 

  71. Ashkenasy, G., Hermans, T. M., Otto, S. & Taylor, A. F. Systems chemistry. Chem. Soc. Rev. 46, 2543–2554 (2017).

    Article  CAS  PubMed  Google Scholar 

  72. Gromski, P. S., Henson, A. B., Granda, J. M. & Cronin, L. How to explore chemical space using algorithms and automation. Nat. Rev. Chem. 3, 119–128 (2019).

    Article  Google Scholar 

  73. Ruiz-Mirazo, K., Briones, C. & de la Escosura, A. Prebiotic systems chemistry: new perspectives for the origins of life. Chem. Rev. 114, 285–366 (2014).

    Article  CAS  PubMed  Google Scholar 

  74. Krishnamurthy, R. Giving rise to life: transition from prebiotic chemistry to protobiology. Acc. Chem. Res. 50, 455–459 (2017).

    Article  CAS  PubMed  Google Scholar 

  75. Kahana, A. & Lancet, D. Protobiotic systems chemistry analyzed by molecular dynamics. Life 9, 38 (2019).

    Article  CAS  PubMed Central  Google Scholar 

  76. Markovitch, O. & Lancet, D. Multispecies population dynamics of prebiotic compositional assemblies. J. Theor. Biol. 357, 26–34 (2014).

    Article  PubMed  Google Scholar 

  77. Shenhav, B., Bar-Even, A., Kafri, R. & Lancet, D. Polymer GARD: computer simulation of covalent bond formation in reproducing molecular assemblies. Orig. Life Evol. Biosph. 35, 111–133 (2005).

    Article  CAS  PubMed  Google Scholar 

  78. Cavalier-Smith, T. Obcells as proto-organisms: membrane heredity, lithophosphorylation, and the origins of the genetic code, the first cells, and photosynthesis. J. Mol. Evol. 53, 555–595 (2001).

    Article  CAS  PubMed  Google Scholar 

  79. Cavalier-Smith, T. in Organelles, Genomes and Eukaryote Phylogeny: An Evolutionary Synthesis in the Age of Genomics (eds Hirt, R. P. & Horner, D. S.) 335–351 (CRC, 2004).

  80. Blobel, G. Intracellular protein topogenesis. Proc. Natl Acad. Sci. USA 77, 1496–1500 (1980).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Loskot, P., Atitey, K. & Mihaylova, L. Comprehensive review of models and methods for inferences in bio-chemical reaction networks. Front. Genet. 10, 549 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Andersen, M., Panosetti, C. & Reuter, K. A practical guide to surface kinetic Monte Carlo simulations. Front. Chem. 7, 202 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Hordijk, W. Evolution of autocatalytic sets in computational models of chemical reaction networks. Orig. Life Evol. Biosph. 46, 233–245 (2016).

    Article  CAS  PubMed  Google Scholar 

  84. Segrè, D., Shenhav, B., Kafri, R. & Lancet, D. The molecular roots of compositional inheritance. J. Theor. Biol. 213, 481–491 (2001).

    Article  PubMed  CAS  Google Scholar 

  85. Sharov, A. A. Coenzyme world model of the origin of life. Biosystems 144, 8–17 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Segrè, D. & Lancet, D. Composing life. EMBO Rep. 1, 217–222 (2000).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Ravoni, A. Long-term behaviours of autocatalytic sets. J. Theor. Biol. 529, 110860 (2021).

    Article  PubMed  CAS  Google Scholar 

  88. Wong, A. S. Y. & Huck, W. T. S. Grip on complexity in chemical reaction networks. Beilstein J. Org. Chem. 13, 1486–1497 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Blokhuis, A., Lacoste, D. & Nghe, P. Universal motifs and the diversity of autocatalytic systems. Proc. Natl Acad. Sci. USA 117, 25230–25236 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Kafri, M., Metzl-Raz, E., Jonas, F. & Barkai, N. Rethinking cell growth models. FEMS Yeast Res. 16, fow081 (2016).

    Article  PubMed  CAS  Google Scholar 

  91. Opaliński, Ł., Veenhuis, M. & Van der Klei, I. J. Peroxisomes: membrane events accompanying peroxisome proliferation. Int. J. Biochem. Cell Biol. 43, 847–851 (2011).

    Article  PubMed  CAS  Google Scholar 

  92. Liu, Y. On the definition of a self-sustaining chemical reaction system and its role in heredity. Biol. Direct 15, 15 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Vasas, V., Fernando, C., Santos, M., Kauffman, S. & Szathmáry, E. Evolution before genes. Biol. Direct 7, 1 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  94. Inger, A., Solomon, A., Shenhav, B., Olender, T. & Lancet, D. Mutations and lethality in simulated prebiotic networks. J. Mol. Evol. 69, 568–578 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Gross, R., Fouxon, I., Lancet, D. & Markovitch, O. Quasispecies in population of compositional assemblies. BMC Evol. Biol. 14, 265 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Eigen, M., McCaskill, J. & Schuster, P. Molecular quasi-species. J. Phys. Chem. 92, 6881–6891 (1988).

    Article  CAS  Google Scholar 

  97. Solà, J., Jimeno, C. & Alfonso, I. Exploiting complexity to implement function in chemical systems. Chem. Commun. 56, 13273–13286 (2020).

    Article  Google Scholar 

  98. Bonfio, C., Russell, D. A., Green, N., Mariani, A. & Sutherland, J. Activation chemistry drives the emergence of functionalized protocells. Chem. Sci. 11, 10688–10697 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Joshi, M. P., Sawant, A. A. & Rajamani, S. Spontaneous emergence of membrane-forming protoamphiphiles from a lipid–amino acid mixture under wet–dry cycles. Chem. Sci. 12, 2970–2978 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Böhler, C., Hill, A. R. & Orgel, L. E. Catalysis of the oligomerization of O-phospho-serine, aspartic acid, or glutamic acid by cationic micelles. Orig. Life Evol. Biosph. 26, 1–5 (1996).

    Article  PubMed  Google Scholar 

  101. Gabriel, C. M., Keener, M., Gallou, F. & Lipshutz, B. H. Amide and peptide bond formation in water at room temperature. Org. Lett. 17, 3968–3971 (2015).

    Article  CAS  PubMed  Google Scholar 

  102. Kunieda, N., Fuei, N., Okamoto, K., Suzuki, T. & Kinoshita, M. Liquid chromatographic assay of the products from the condensation reaction of α-amino thioacid S-dodecyl ester hydrobromides or hydrochlorides in water. Makromol. Chem. Rapid Commun. 3, 865–869 (1982).

    Article  CAS  Google Scholar 

  103. Jin, S. et al. Traceless native chemical ligation of lipid-modified peptide surfactants by mixed micelle formation. Nat. Commun. 11, 2793 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Raine, D. & Norris, V. Lipid domain boundaries as prebiotic catalysts of peptide bond formation. J. Theor. Biol. 246, 176–185 (2007).

    Article  CAS  PubMed  Google Scholar 

  105. Frenkel-Pinter, M. et al. Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions. Proc. Natl Acad. Sci. USA 116, 16338–16346 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Hassenkam, T., Damer, B., Mednick, G. & Deamer, D. AFM images of viroid-sized rings that self-assemble from mononucleotides through wet–dry cycling: implications for the origin of life. Life 10, 321 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  107. Ross, D. S. & Deamer, D. Dry/wet cycling and the thermodynamics and kinetics of prebiotic polymer synthesis. Life 6, 28 (2016).

    Article  CAS  PubMed Central  Google Scholar 

  108. Müller, U. F. & Bartel, D. P. Improved polymerase ribozyme efficiency on hydrophobic assemblies. RNA 14, 552–562 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Gabdrakhmanov, D. et al. Reactivity of phosphorus esters in supramolecular systems based on surfactants containing an uracil residue and polyethylenimine. Russ. J. Org. Chem. 50, 500–505 (2014).

    Article  CAS  Google Scholar 

  110. Cuomo, F. et al. Molecular interactions mediated by nucleo-base functionalized lipids. J. Surf. Sci. Technol. 31, 59–68 (2015).

    CAS  Google Scholar 

  111. Berti, D., Barbaro, P., Bucci, I. & Baglioni, P. Molecular recognition through H-bonding in micelles formed by dioctylphosphatidyl nucleosides. J. Phys. Chem. B 103, 4916–4922 (1999).

    Article  CAS  Google Scholar 

  112. Sproul, G. Abiogenic syntheses of lipoamino acids and lipopeptides and their prebiotic significance. Orig. Life Evol. Biosph. 45, 427–437 (2015).

    Article  CAS  PubMed  Google Scholar 

  113. Frenkel-Pinter, M., Samanta, M., Ashkenasy, G. & Leman, L. J. Prebiotic peptides: molecular hubs in the origin of life. Chem. Rev. 120, 4707–4765 (2020).

    Article  CAS  PubMed  Google Scholar 

  114. Gibard, C., Bhowmik, S., Karki, M., Kim, E.-K. & Krishnamurthy, R. Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions. Nat. Chem. 10, 212–217 (2018).

    Article  CAS  PubMed  Google Scholar 

  115. Liu, Z. et al. Harnessing chemical energy for the activation and joining of prebiotic building blocks. Nat. Chem. 12, 1023–1028 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Piast, R. W., Garstka, M., Misicka, A. & Wieczorek, R. M. Small cyclic peptide for pyrophosphate dependent ligation in prebiotic environments. Life 10, 103 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  117. Fattal, D. R., Andelman, D. & Ben-Shaul, A. The vesicle-micelle transition in mixed lipid-surfactant systems: a molecular model. Langmuir 11, 1154–1161 (1995).

    Article  CAS  Google Scholar 

  118. Conde-Frieboes, K. & Blöchliger, E. Synthesis of lipids on the micelle/water interface using inorganic phosphate and an alkene oxide. Biosystems 61, 109–114 (2001).

    Article  CAS  PubMed  Google Scholar 

  119. Mizuhashi, T., Asakawa, T. & Ohta, A. Micelle–vesicle transition by cleavage of disulfide spacer chain for gemini surfactant in didodecyldimethylammonium chloride aqueous solutions. J. Oleo Sci. 64, 963–969 (2015).

    Article  CAS  PubMed  Google Scholar 

  120. Albertsen, A. N., Maurer, S., Nielsen, K. & Monnard, P.-A. Transmission of photo-catalytic function in a self-replicating chemical system: in situ amphiphile production over two protocell generations. Chem. Commun. 50, 8989–8992 (2014).

    Article  CAS  Google Scholar 

  121. Chen, I. A. & Szostak, J. W. A kinetic study of the growth of fatty acid vesicles. Biophys. J. 87, 988–998 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Budin, I. & Szostak, J. W. Physical effects underlying the transition from primitive to modern cell membranes. Proc. Natl Acad. Sci. USA 108, 5249–5254 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Jin, L., Kamat, N. P., Jena, S. & Szostak, J. W. Fatty acid/phospholipid blended membranes: a potential intermediate state in protocellular evolution. Small 14, 1704077 (2018).

    Article  CAS  Google Scholar 

  124. Nowak, M. A. & Ohtsuki, H. Prevolutionary dynamics and the origin of evolution. Proc. Natl Acad. Sci. USA 105, 14924–14927 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Clarke, B. L. & Jeffries, C. Chemical reaction networks with finite attractor regions. J. Chem. Phys. 82, 3107–3117 (1985).

    Article  CAS  Google Scholar 

  126. Harrison, A., Zeevi, M. P., Vasey, C. L., Nguyen, M. D. & Tang, C. Accelerated reaction rates within self-assembled polymer nanoreactors with tunable hydrophobic microenvironments. Polymers 12, 1774 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  127. Kunitake, T., Okahata, Y. & Sakamoto, T. Multifunctional hydrolytic catalyses. 8. Remarkable acceleration of the hydrolysis of p-nitrophenyl acetate by micellar bifunctional catalysts. J. Am. Chem. Soc. 98, 7799–7806 (1976).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Minerva Foundation through the grant “The emergence and evolution of early life under extreme planetary conditions” and by an EU Horizon 2020 (DC-ren) grant (Drug combinations for rewriting trajectories of renal pathologies in type II diabetes). The authors thank D. Segrè, D. Tawfik and A. Futerman for critically reading the manuscript.

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Glossary

Accretion

Gradual growth in size by external addition.

Breed true

Producing offspring of a similar breed or variety.

Catalytic closure

A state of a molecular network where the formation of each molecule in the set is catalysed by at least one set member.

Fission

A splitting or breaking up into parts.

Gemini lipid

A class of lipids containing two head groups and two aliphatic tails linked by a spacer.

Palisade layer

The border region between the polar head groups and the hydrophobic core.

Parsimonious

Related to the simplest explanation of a phenomenon.

Prebiotic

Occurring or existing before the emergence of life.

Primordial

Ancient, existing from the beginning.

Quasispecies

A group of highly similar molecules or organisms.

Reduced dimensionality

A phenomenon in which reactions are speeded up by reactants adsorbing to a 2D surface.

Stern layer

The immediate proximity of the micellar surface.

Terrestrial infall

Incoming extraterrestrial material that falls on Earth.

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Kahana, A., Lancet, D. Self-reproducing catalytic micelles as nanoscopic protocell precursors. Nat Rev Chem 5, 870–878 (2021). https://doi.org/10.1038/s41570-021-00329-7

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