Stabilization of prebiotic vesicles by peptides depends on sequence and chirality

Abstract Life depends on homochiral oligomers with specific sequences to carry out essential functions. How could such oligomers have been selected from the prebiotic clutter? What was the first function for which sequences were selected? Cells were probably preceded by simple compartments, such as fatty acid vesicles, composed of a membrane and one or more oligomers. Differential stabilization of such vesicles could have been the key to answering these questions. Oligomers that increased stability and/or growth of the membrane would have conferred an advantage to vesicles competing for limited membrane components. We therefore tested whether prebiotic peptides (simple oligomers) alter the stability or growth of vesicles composed of a prebiotic fatty acid. We find that one of the peptides, leucine-leucine (Leu-Leu), rapidly shrinks the vesicles and makes them leakier when heterochiral (either L-D or D-L), but not when homochiral (either L-L or D-D). Testing for effects on salt-induced flocculation of vesicles, we find three of fifteen dipeptides reduce flocculation. All three contain leucine, and increasing length increases efficacy. In a final test for modulation of vesicle properties, we find two leucine-containing peptides that increase the size of fatty acid vesicles grown by multiple additions of fatty acid micelles, and a tripeptide outperforms a dipeptide. Thus, prebiotic peptides influence the size, leakiness, susceptibility to flocculation, and growth of prebiotic vesicles and do so with specificity for chirality, sequence, and length. Vesicles that bound peptides favoring stability and/or growth could have outcompeted other vesicles for lipid components of the membrane, beginning selection for the functional oligomers that underpin life.