Liquid-Liquid Phase Separation of Inorganic Polyphosphate; the Complexities of a Simple Model

Inorganic polyphosphate (polyP) is a widely conserved primordial biological anion which is present in every branch of life. However, a thorough description of its biophysical properties is lacking. This fundamental research is crucial and could illuminate not only the biological role of polyP but lead to greater understanding of the biophysical properties of DNA and RNA, of which polyP forms a major component of the background. By understanding the contribution of polyP to the properties of the nucleic acids, we can better isolate base-dependent properties. This will contribute greatly to efforts such as bio-engineering and medicine. Here, we will present data depicting the phase behavior of polyP, showing that it forms a wide variety of condensates through liquid-liquid phase separation with numerous cations, including divalent salts, polyamines, and proteins. These condensates show a stunning variety of properties, ranging from gel-like to fully liquid. Most intriguingly, the majority of these condensates are reentrant, and dissolve upon concentration fluctuations of polyP or cations. This reentrant, surprisingly complex and richly diverse phase behavior is important as a model for more complex protein-RNA granules and in vivo membraneless organelles.