One challenge associated with building a life-like synthetic cell lies in how to power synthetic cell processes. A common mechanism used by natural cells to energize cell activities is the exploitation of an electrochemical gradient across a membrane. This grant funds a project led by Neal Devaraj at the University of California, San Diego to build an artificial system that couples the formation and maintenance of a pH gradient with anabolic chemistry to establish a primitive metabolism in a synthetic cell. Devaraj and his team will use photoacids encapsulated in lipid vesicles as the primitive protocells of this project. The photoacids release hydrogen ions (protons) when exposed to light, leading to an excess of protons within the vesicle. Reagent molecules will diffuse into the vesicle from the surrounding “environment” and become trapped as they acquire an electrical charge by bonding with hydrogen ions inside the proton-rich vesicle. These charged molecules will accumulate within the vesicle due to so-called ion-trapping, a phenomenon whereby a membrane that is permeable to neutral molecules becomes impermeable to charged molecules. The concentrating of reagent molecules within the vesicle will then stimulate an anabolic reaction: synthesis of phospholipids. The synthesized phospholipid molecules are building blocks for cell membranes and developing ways to synthesize these building blocks could prove useful for future efforts to build artificial cells that must be able to grow and divide. Devaraj expects that the synthesized lipids will—driven by hydrophobic interactions—associate into and thereby modify the pre-existing vesicle membrane. Microscopy will be used to characterize changes in membrane morphology, changes that could include membrane growth and division.