Modulation of Biomolecular Liquid-Liquid Phase Separation by Preferential Hydration and Interaction of Small Osmolytes with Proteins.

We examined the effects of trimethylamine -oxide (TMAO) and urea (known osmolytes) on the liquid-liquid phase separation (LLPS) of fused in sarcoma (FUS) and three FUS-LLPS states: LLPS states at atmospheric pressure with low- and high-salt concentrations and a re-entrant LLPS state above 2 kbar. Temperature- and pressure-scan turbidity measurements revealed that TMAO and urea contributed to stabilizing and destabilizing LLPS, respectively. These results can be attributed to the excluded volume effect of TMAO (preferential hydration) and preferential interaction of urea with proteins.

Mechanism underlying liquid-to-solid phase transition in fused in sarcoma liquid droplets.

The RNA-binding protein fused in sarcoma (FUS) forms ribonucleoprotein granules liquid-liquid phase separation (LLPS) in the cytoplasm. The phase separation of FUS accelerates aberrant liquid-solid phase separation and leads to the onset of familial amyotrophic lateral sclerosis (ALS). We previously found that FUS forms two types of liquid condensates in equilibrium, specifically LP-LLPS (, normal type) and HP-LLPS (, aberrant type), each with different partial molar volumes.