This work is presented as a Hypothesis Article, offering a conceptual framework that integrates prebiotic chemistry, simulation data, and modern peptide analogues to propose β-strand oligomers as a plausible solution to the protocell permeability problem. A persistent challenge in origins-of-life research is explaining how primitive fatty-acid vesicles could exchange molecules with their surroundings. While such compartments assemble readily under prebiotic conditions, they are largely impermeable to nucleotides, peptides, and divalent ions, risking chemical isolation. Here, I evaluate the hypothesis that short, abiotically produced β-strand peptides could have modulated protocell permeability. Unlike α-helical pore formers, which require helix-stabilizing residues rare in prebiotic syntheses, β-strand oligomers are strongly favored by the glycine-, alanine-, and valine rich inventories documented in meteorites and laboratory experiments. These sequences are also known to form amyloid-like aggregates that introduce leaky defects into bilayers. Environmental cycles such as dehydration, rehydration, eutectic freezing, and high-salt vent chemistries would have promoted such assemblies, and peptide libraries derived from stochastic simulations reveal amphipathic motifs consistent with aggregation. Taken together, these results suggest that irregular β-sheet oligomers may have provided the first, non-selective permeability in fatty-acid protocells. This hypothesis is testable; Gly/Ala/Val-rich peptides synthesized under prebiotic cycling conditions should measurably increase leakage across fatty-acid vesicles, providing a tractable experimental framework for probing early membrane function.
Arda Sems (2025) studied this question.