# Organocatalyzed bottom-up formation of protocells

**Authors:** Marian Simon Rafael Ebeling, Otto Berninghausen, Khang Hoang Nguyen, Roland Beckmann, Oliver Trapp

PMC · DOI: 10.1038/s41467-026-69597-5 · Nature Communications · 2026-02-23

## TL;DR

Scientists created protocells using a chemical process that starts with simple prebiotic molecules, forming lipid-like structures that self-assemble into cell-like compartments.

## Contribution

A novel organocatalytic pathway is introduced for the bottom-up formation of protocells from prebiotically plausible molecules.

## Key findings

- An organocatalytic reaction cascade produces lipid-like molecules that self-assemble into protocells.
- The resulting protocells are stable under various environmental conditions like pH, temperature, and salt.
- The process does not require preformed amphiphiles, offering a plausible prebiotic mechanism for compartmentalization.

## Abstract

The organisation of living systems into cellular structures is a characteristic that enables differentiation from the environment. A pivotal step in the development of life is compartmentalisation, achieved through the formation of vesicle-like structures. Fatty acids - or phospholipids - have been used to simulate prebiotic vesicle and protocell formation. However, a process by which amphiphiles are formed from small prebiotically plausible molecules, which spontaneously self-assemble to protocells, is unknown. Here, we demonstrate that an organocatalytic reaction cascade starting from acetaldehyde with prebiotic imidazolidine-4-thione rapidly yields poly(hydroxy)alkenyl aldehydes that spontaneously self-assemble to protocells. In this process, lipid-like molecules (up to C20) develop a membrane, which additionally incorporates the organocatalyst at the liquid-lipid interface. These catalytically active protocells (11 nm – 7 μm) tolerate external influences such as pH value, temperature and salts. This finding unveils an organocatalytic pathway to selective lipid formation and spontaneous compartmentalisation without the necessity of preformed amphiphiles.

Compartmentalization via amphiphilic compounds was crucial for life’s emergence. In a bottom-up approach, the authors used organocatalysis to generate aldol oligomers that incorporated the catalyst as a polar head group, forming vesicle structures.

## Linked entities

- **Chemicals:** acetaldehyde (PubChem CID 177), imidazolidine-4-thione (PubChem CID 21916658)

## Full-text entities

- **Genes:** FASN (fatty acid synthase) [NCBI Gene 2194] {aka FAS, OA-519, SDR27X1}, GTPBP1 (GTP binding protein 1) [NCBI Gene 9567] {aka GP-1, GP1, HSPC018, NEDFET1}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}
- **Chemicals:** CO2 (MESH:D002245), C2 (MESH:C023714), polyenes (MESH:D011090), Lipid (MESH:D008055), Lawesson's reagent (MESH:C029887), THF (MESH:C018674), Na2CO3 (MESH:C005686), LDA (MESH:C007442), resin (MESH:D012116), n-pentane (MESH:C033353), alcohols (MESH:D000438), cyanides (MESH:D003486), H (MESH:D006859), Acetaldehyde (MESH:D000079), rhodamine B (MESH:C029773), formaldehyde (MESH:D005557), decanoic acid (MESH:C031071), argon (MESH:D001128), (E)-3-((tert-butyldimethylsilyl)oxy)hex-4-enal (-), ethyl acetate (MESH:C007650), NaHCO3 (MESH:D017693), montmorillonite (MESH:D001546), H2S (MESH:D006862), HE (MESH:D006371), toluene (MESH:D014050), Na2SO4 (MESH:C012036), DIBALH (MESH:C035719), amino acids (MESH:D000596), MgSO4 (MESH:D008278), uranyl acetate (MESH:C005460), amine (MESH:D000588), phosphatidylcholines (MESH:D010713), Oil (MESH:D009821), Fatty acids (MESH:D005227), phospholipids (MESH:D010743), H2O (MESH:D014867), Imidazole (MESH:C029899), acetyl-CoA (MESH:D000105), iron (MESH:D007501), cation (MESH:D002412), n-BuLi (MESH:C434823), malonyl-CoA (MESH:D008316), alkanes (MESH:D000473), CaCl2 (MESH:D002122), acetic acid (MESH:D019342), HCl (MESH:D006851), NaOH (MESH:D012972), aldehyde (MESH:D000447), MgCl2 (MESH:D015636), geranylgeraniol (MESH:C017338), NaCl (MESH:D012965), sugars (MESH:D000073893), magnetite (MESH:D052203), phosphates (MESH:D010710), salt (MESH:D012492), O (MESH:D010100), NH3 (MESH:D000641), polysaccharides (MESH:D011134), polyols (MESH:C024617), NH4Cl (MESH:D000643)

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932765/full.md

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Source: https://tomesphere.com/paper/PMC12932765