From Meteorites to Membrane Rafts: Ganglioside-Incorporating Prebiotic Vesicles and the Emergence of Membrane Domain Organization.

Life requires membranes. But what were the first membranes made of, and how did they acquire the functional complexity of modern cells? Here we show that nonanoic acid and nonanol, two short-chain amphiphiles found in carbonaceous meteorites, spontaneously incorporate gangliosides into their membranes, generating a ternary vesicle system that, under prebiotic-inspired conditions, recapitulates three hallmarks of eukaryotic membrane biology: (i) lateral membrane domain segregation consistent with lateral compositional heterogeneity analogous to liquid-ordered and liquid-disordered phase co-existence; (ii) ganglioside-dependent and charge-selective capture of cationic peptides, confirmed by both centrifugation-binding assays and Langmuir monolayer experiments; and (iii) inward membrane budding and intraluminal vesicle formation upon cationic peptide treatment, recapitulating multivesicular body biogenesis in a minimal molecular system. Molecular modeling reveals that the nonanoic acid/nonanol pair occupies a molecular volume equivalent to the sterane core of cholesterol, explaining its cholesterol-surrogate function. These findings demonstrate that lateral domain segregation, surface glycolipid asymmetry, and endocytic membrane remodeling are not evolutionary inventions; they are emergent physicochemical properties of amphiphile-glycolipid systems that predate cellular life itself.