PT - JOURNAL ARTICLE AU - Ghosh, Archishman AU - Zhang, Xiaojia AU - Zhou, Huan-Xiang TI - A Tug of War Between Condensate Phases in a Minimal Macromolecular System AID - 10.1101/2020.01.29.925099 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.01.29.925099 4099 - http://biorxiv.org/content/early/2020/01/30/2020.01.29.925099.short 4100 - http://biorxiv.org/content/early/2020/01/30/2020.01.29.925099.full AB - Membraneless organelles formed via liquid-liquid phase separation (LLPS) contain a multitude of macromolecular species. A few of these species drive LLPS while most serve as regulators. The LLPS of SH35 (S) and PRM5 (P), two oppositely charged protein constructs, was promoted by a polyanion heparin (H) but suppressed by a cationic protein lysozyme (L). Here, using these four components alone, we demonstrate complex phase behaviors associated with membraneless organelles and uncover the underlying physical rules. The S:P, S:L, and P:H binaries form droplets, but the H:L binary forms precipitates, therefore setting off a tug of water between different phases within the S:P:H:L quaternary. We observe dissolution of precipitates upon compositional change, transformation from precipitates to droplet-like condensates over time, and segregation of S:L-rich and P:H-rich foci inside droplet-like condensates. A minimal macromolecular system can thus recapitulate membraneless organelles in essential ways and provide crucial physical understanding.