Repulsive Electrostatic Interactions Modulate Dense and Dilute Phase Properties of Biomolecular Condensates

Liquid-like membraneless organelles form via multiple, weak interactions between biomolecules. The resulting condensed states constitute novel solvent environments inside eukaryotic cells that partition biomolecules and may favour particular biochemical reactions. Here we demonstrate that, in addition to attractive interactions, repulsive electrostatic interactions modulate condensate properties. We find that net charge modulates the formation, morphology and solvent properties of model Ddx4 condensates in cells and in vitro and that a net negative charge is conserved across germ cell-specific Ddx4 orthologues. This conserved net charge provides a sensitivity to multivalent cations that is not observed in somatic paralogues. The disfavouring effect of a net negative charge in Ddx4 orthologues appears to be offset by increased charge patterning, indicating that fine tuning of both attractive and repulsive interactions can create responsive solvent environments inside biomolecular condensates.