Origin of electroneutrality in living system

Identifying the first chemical transformations, from which life emerged is a central problem in the theories of life’s origins. These reactions would likely have been self-sustaining and self-reproductive before the advent of complex biochemical pathways found in modern organisms to synthesize lipid membranes, enzymes, or nucleic acids. Without lipid membranes and enzymes, exceedingly low concentrations of the organic intermediates of early metabolic cycles in protocells would have significantly hindered evolvability. To address this problem, we propose a mechanism, where a positive membrane potential elevates the concentration of the organic intermediates. In this mechanism, positively charged surfaces of protocell membranes due to accumulation of transition metals generate positive membrane potentials. We compute steady-state ion distributions and determine their stability in a protocell model to identify the key factors constraining achievable membrane potentials. We find that (i) violation of electroneutrality is necessary to induce nonzero membrane potentials; (ii) strategies that generate larger membrane potentials can destabilize ion distributions; and (iii) violation of electroneutrality enhances osmotic pressure and diminishes reaction efficiency, thereby driving the evolution of lipid membranes, specialized ion channels, and active transport systems. Significance The building blocks of life are constantly synthesized and broken down through concurrent cycles of chemical transformations. Tracing these reactions back 4 billion years to their origins has been a long-standing goal of evolutionary biology. The first metabolic cycles at the origin of life must have overcome several obstacles to spontaneously start and sustain their nonequilibrium states. Notably, maintaining the concentration of organic intermediates at high levels needed to support their continued operation and subsequent evolution would have been particularly challenging in primitive cells lacking evolutionarily tuned lipid membranes and enzymes. Here, we propose a mechanism, in which the concentration of organic intermediates could have been elevated to drive early metabolic cycles forward in primitive cells with ion-permeable porous membranes under prebiotic conditions and demonstrate its feasibility in a protocell model from first principles.