Biomolecular\nCondensates are Characterized by Interphase\nElectric Potentials

Biomolecular\ncondensates form via processes that combine phase\nseparation and reversible associations of multivalent macromolecules.\nCondensates can be two- or multiphase systems defined by coexisting\ndense and dilute phases. Here, we show that solution ions partition\nasymmetrically across coexisting phases defined by condensates formed\nby intrinsically disordered proteins or homopolymeric RNA molecules.\nOur findings were enabled by direct measurements of the activities\nof cations and anions within coexisting phases of protein and RNA\ncondensates. Asymmetries in ion partitioning between coexisting phases\nvary with protein sequence, macromolecular composition, salt concentration,\nand ion type. The Donnan equilibrium set up by the asymmetrical partitioning\nof solution ions generates interphase electric potentials known as\nDonnan and Nernst potentials. Our measurements show that the interphase\npotentials of condensates are of the same order of magnitude as membrane\npotentials of membrane-bound organelles. Interphase potentials quantify\nthe degree to which microenvironments of coexisting phases are different\nfrom one another. Importantly, and based on condensate-specific interphase\nelectric potentials, we reason that condensates are akin to capacitors\nthat store charge. Interphase potentials should lead to electric double\nlayers at condensate interfaces, thereby explaining recent observations\nof condensate interfaces being electrochemically active.