Proliferating coacervate droplets as the missing link between chemistry and biology in the origins of life

Coacervate droplets (CDs) are a model for protocells formed by liquid-liquid phase separation (LLPS), but protocell models able to proliferate remain undeveloped. Here, the authors report a proliferating peptide-based CD using synthesised amino acid thioesters as monomers, which could concentrate RNA and lipids, enabling RNA to protect the droplet from dissolution by lipids. The hypothesis that prebiotic molecules were transformed into polymers that evolved into proliferating molecular assemblages and eventually a primitive cell was first proposed about 100 years ago. To the best of our knowledge, however, no model of a proliferating prebiotic system has yet been realised because different conditions are required for polymer generation and self-assembly. In this study, we identify conditions suitable for concurrent peptide generation and self-assembly, and we show how a proliferating peptide-based droplet could be created by using synthesised amino acid thioesters as prebiotic monomers. Oligopeptides generated from the monomers spontaneously formed droplets through liquid-liquid phase separation in water. The droplets underwent a steady growth-division cycle by periodic addition of monomers through autocatalytic self-reproduction. Heterogeneous enrichment of RNA and lipids within droplets enabled RNA to protect the droplet from dissolution by lipids. These results provide experimental constructs for origins-of-life research and open up directions in the development of peptide-based materials.