Acyl Phosphates as Chemically Fueled Building Blocks for Self-Sustaining Protocells.

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.

Fuel-Driven Dynamic Combinatorial Libraries.

In dynamic combinatorial libraries, molecules react with each other reversibly to form intricate networks under thermodynamic control. In biological systems, chemical reaction networks operate under kinetic control by the transduction of chemical energy. We thus introduced the notion of energy transduction, via chemical reaction cycles, to a dynamic combinatorial library. In the library, monomers can be oligomerized, oligomers can be deoligomerized, and oligomers can recombine. Interestingly, we found that the dynamics of the library's components were dominated by transacylation, which is an equilibrium reaction. In contrast, the library's dynamics were dictated by fuel-driven activation, which is a nonequilibrium reaction. Finally, we found that self-assembly can play a large role in affecting the reaction's kinetics via feedback mechanisms. The interplay of the simultaneously operating reactions and feedback mechanisms can result in hysteresis effects in which the outcome of the competition for fuel depends on events that occurred in the past. In future work, we envision diversifying the library by modifying building blocks with catalytically active motifs and information-containing monomers.