Growth of fatty acid vesicles coupled with amino acid sequences of peptides toward evolvable protocells

Understanding how genetic polymer sequences became coupled with the reproduction of protocellular compartments is a fundamental challenge in the study of the emergence of living systems. Here, we demonstrate that the coexistence of peptides with defined amino acid sequences and fatty acid vesicles can establish a primitive form of this coupling. We prepared systematically sequence-controlled peptides and examined how their sequences influence the growth rate (fitness) of fatty acid vesicles. The growth of fatty acid vesicles was estimated by dynamic light scattering (DLS) and cryogenic transmission electron microscopic techniques when fatty acid molecules and peptides were fed into a fatty acid vesicle suspension. The relationship between amino acid sequences of peptides and vesicle growth rate was visualized as a fitness landscape, which reveals that specific amino acid sequences promote vesicle growth significantly. Furthermore, we observed epistasis, where the effect of amino acid residue replacement on the fitness depends on the remaining amino acid sequence. Finally, we show that vesicle growth is thermodynamically driven by peptide-induced modulation of the chemical potential of fatty acid molecules. These findings provide direct experimental evidence that primitive sequence information can become spontaneously coupled to vesicle growth.