Monovalent Ion Effect on Liquid–Liquid Phase Separation of Aqueous Polyphosphate–Salt Mixtures

Polyphosphate (polyP) is one of the most conserved biomacromolecules and can form aggregates, such as polyP granules in bacteria, which are generated through liquid-liquid phase separation (LLPS). Studies have examined the mechanism of polyP aggregation using LLPS systems containing artificial polyP molecules as aggregation system models, where LLPS is typically induced by multivalent salts and polyelectrolytes. Although the typical concentrations of monovalent ions in living cells are approximately 100 times higher than those of divalent ions, the effects of monovalent ions on the LLPS of polyP solutions are little known. This study demonstrated that submolar NaCl induces LLPS of polyP solutions, whereas other monovalent salts did not induce LLPS at the same concentrations. Small-angle X-ray scattering measurements revealed that NaCl significantly stabilizes the intermolecular association of polyP, inducing LLPS. These findings suggest that the modulation of monovalent ion concentrations is an underlying mechanism of polyP aggregate formation and deformation within living cells.