Spontaneous Crowding of Ribosomes and Proteins inside Vesicles: A Possible Mechanism for the Origin of Cell Metabolism

One of the open questions in the origin of life is the spontaneous formation of primitive cell-like compartments from free molecules in solution and membranes. Metabolism-first and replicator-first theories claim that early catalytic cycles first evolved in solution, and became encapsulated inside lipid vesicles later on. Compartment-first theories suggest that metabolism progressively occurred inside compartments. Both views have some weaknesses: the low probability of co-entrapment of several compounds inside the same compartment, and the need to control nutrient uptake and waste release, respectively. By using lipid vesicles as early-cell models, we show that ribosomes, proteins and lipids spontaneously self-organise into cell-like compartments to achieve high internal concentrations, even when starting from dilute solutions. These findings suggest that the assembly of cell-like compartments, despite its low probability of occurrence, is indeed a physically realistic process. The spontaneous achievement of high local concentration might provide a rational account for the origin of primitive cellular metabolism.