Acyl Phosphates as Chemically Fueled Building Blocks for Self‐Sustaining Protocells

Abstract Lipids spontaneously assemble into vesicle‐forming membranes. Such vesicles serve as compartments for even the simplest living systems. Vesicles have been extensively studied for constructing synthetic cells or as models for protocells—the cells hypothesized to have existed before life. These compartments exist almost always close to equilibrium. Life, however, exists out of equilibrium. In this work, we studied vesicle‐based compartments regulated by a non‐equilibrium chemical reaction network that converts activating agents. In this way, the compartments require a constant or periodic supply of activating agents to sustain themselves. Specifically, we use activating agents to condense carboxylates and phosphate esters into acyl phosphate‐based lipids that form vesicles. These vesicles can only be sustained when condensing agents are present; without them, they decay. We demonstrate that the chemical reaction network can operate on prebiotic activating agents, opening the door to prebiotically plausible, self‐sustainable protocells that compete for resources. In future work, such protocells should be endowed with a genotype, e.g., self‐replicating RNA structures, to alter the protocell's behavior. Such protocells could enable Darwinian evolution in a prebiotically plausible chemical system.