Aging-dependent evolving electrochemical potentials of biomolecular condensates regulate their physicochemical activities

A passive consequence of macromolecular condensation is the establishment of an ion concentration gradient between the dilute and dense phases, which in turn governs distinct electrochemical properties of condensates. However, the mechanisms that regulate the electrochemical equilibrium of condensates and their impacts on emergent physicochemical functions remain unknown. Here we demonstrate that the electrochemical environments and the physical and chemical activities of biomolecular condensates, dependent on the electrochemical potential of condensates, are regulated by aging-associated intermolecular interactions and interfacial effects. Our findings reveal that enhanced dense-phase interactions during condensate maturation continuously modulate the ion distribution between the two phases. Moreover, modulating the interfacial regions of condensates can affect the apparent pH within the condensates. To directly probe the interphase and interfacial electric potentials of condensates, we have designed and implemented electrochemical potentiometry and second harmonic generation-based approaches. Our results suggest that the non-equilibrium nature of biomolecular condensates might play a crucial role in modulating the electrochemical activities of living systems. (Figure presented.)