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PreprintCC BYChemRxiv

Growth-Triggered Nano-vesicle Budding via Leaflet Area Asymmetry in Fatty-Acid Protocells

Abstract

Fatty-acid vesicles growing by monomer uptake, as demonstrated experimentally for Szostak-type protocells, insert new amphiphiles predominantly into the outer leaflet. Because transbilayer flip-flop is not instantaneous, this generates a growing area mismatch between the two leaflets. We show, using the area-difference-elasticity (ADE) framework for vesicle shape, that this mismatch crosses a threshold beyond which the vesicle relieves it by shedding small, high-curvature nano-vesicles rather than by symmetric division–with no external mechanical forcing required. A leaflet-resolved kinetic model shows that sustained parent growth over many such cycles requires the shed nano-vesicles to be compositionally enriched in the destabilizing (outer-leaflet) material rather than ordinary bilayer: a specific, falsifiable prediction. For illustrative growth and flipflop rates the model predicts nano-vesicles of radius 60–90 nm, above the stability floor of fatty-acid vesicles. This mechanism, and its central prediction, match independent experimental observations on fatty-acid and lysolipid-containing vesicles. In an earlier work [1] we explored periodic environmental mechanical forcing (tidal, geyser and vortex-driven shear) as an alternative trigger for vesicle instability; that mechanism rests on poorly constrained assumptions about Hadean orbital dynamics and produces, in its simplest form, no resonance, only a low-pass response. The present mechanism requires no assumption about the early Earth’s mechanical environment at all.

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BibTeX
@misc{mikulas2026growthtriggered,
  title = {{Growth-Triggered Nano-vesicle Budding via Leaflet Area Asymmetry in Fatty-Acid Protocells}},
  author = {Peter Mikuláš},
  howpublished = {ChemRxiv},
  year = {2026},
  month = oct,
  doi = {10.26434/chemrxiv.15010013/v1},
  url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010013/v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - Growth-Triggered Nano-vesicle Budding via Leaflet Area Asymmetry in Fatty-Acid Protocells
AU  - Peter Mikuláš
PY  - 2026
DA  - 2026/10/07
PB  - ChemRxiv
DO  - 10.26434/chemrxiv.15010013/v1
UR  - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010013/v1
AB  - Fatty-acid vesicles growing by monomer uptake, as demonstrated experimentally for Szostak-type protocells, insert new amphiphiles predominantly into the outer leaflet. Because transbilayer flip-flop is not instantaneous, this generates a growing area mismatch between the two leaflets. We show, using the area-difference-elasticity (ADE) framework for vesicle shape, that this mismatch crosses a threshold beyond which the vesicle relieves it by shedding small, high-curvature nano-vesicles rather than by symmetric division–with no external mechanical forcing required. A leaflet-resolved kinetic model shows that sustained parent growth over many such cycles requires the shed nano-vesicles to be compositionally enriched in the destabilizing (outer-leaflet) material rather than ordinary bilayer: a specific, falsifiable prediction. For illustrative growth and flipflop rates the model predicts nano-vesicles of radius 60–90 nm, above the stability floor of fatty-acid vesicles. This mechanism, and its central prediction, match independent experimental observations on fatty-acid and lysolipid-containing vesicles. In an earlier work [1] we explored periodic environmental mechanical forcing (tidal, geyser and vortex-driven shear) as an alternative trigger for vesicle instability; that mechanism rests on poorly constrained assumptions about Hadean orbital dynamics and produces, in its simplest form, no resonance, only a low-pass response. The present mechanism requires no assumption about the early Earth’s mechanical environment at all.
ER  -