biostudies-literatureAkbari ANational Institutes of HealthNovo Nordisk FondenNIGMS NIH HHSe1010377https://www.ebi.ac.uk/biostudies/studies/S-EPMC9423644biostudies-literatureUnknown18(8)Identifying plausible mechanisms for compartmentalization and accumulation of the organic intermediates of early metabolic cycles in primitive cells has been a major challenge in theories of life's origins. Here, we propose a mechanism, where positive membrane potentials elevate the concentration of the organic intermediates. Positive membrane potentials are generated by positively charged surfaces of protocell membranes due to accumulation of transition metals. We find that (i) positive membrane potentials comparable in magnitude to those of modern cells can increase the concentration of the organic intermediates by several orders of magnitude; (ii) generation of large membrane potentials destabilize ion distributions; (iii) violation of electroneutrality is necessary to induce nonzero mePLoS computational biologyPositively charged mineral surfaces promoted the accumulation of organic intermediates at the origin of metabolism.PMC9423644GM057089R01 GM057089NNF10CC1016517Palsson BOAkbari AfalsePositively charged mineral surfaces promoted the accumulation of organic intermediates at the origin of metabolism.Identifying plausible mechanisms for compartmentalization and accumulation of the organic intermediates of early metabolic cycles in primitive cells has been a major challenge in theories of life's origins. Here, we propose a mechanism, where positive membrane potentials elevate the concentration of the organic intermediates. Positive membrane potentials are generated by positively charged surfaces of protocell membranes due to accumulation of transition metals. We find that (i) positive membrane potentials comparable in magnitude to those of modern cells can increase the concentration of the organic intermediates by several orders of magnitude; (ii) generation of large membrane potentials destabilize ion distributions; (iii) violation of electroneutrality is necessary to induce nonzero me2022-01-01T00:00:00Z2022 Aug2025-04-27T03:18:40.994Z2025-04-06T18:48:42.744ZS-EPMC94236443597697310.1371/journal.pcbi.1010377