Acyl phosphates as chemically fueled building blocks for self-sustaining protocells.

Lipids can 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. Specifically, we use activating agents to condense carboxylates and phosphate esters into acylphosphate-based lipids that form vesicles. These vesicles can only be sustained when condensing agents are present, and 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, for example, based on self-replicating RNA structures that affect the protocell behavior to enable Darwinian evolution in a prebiotically plausible chemical system.