TY - JOUR TI - Narrow equilibrium window for complex coacervation of tau and RNA under cellular conditions AU - Lin, Yanxian AU - McCarty, James AU - Rauch, Jennifer N AU - Delaney, Kris T AU - Kosik, Kenneth S AU - Fredrickson, Glenn H AU - Shea, Joan-Emma AU - Han, Songi A2 - Shan, Yibing A2 - Barkai, Naama A2 - Castaneda, Carlos VL - 8 PY - 2019 DA - 2019/04/05 SP - e42571 C1 - eLife 2019;8:e42571 DO - 10.7554/eLife.42571 UR - https://doi.org/10.7554/eLife.42571 AB - The mechanism that leads to liquid-liquid phase separation (LLPS) of the tau protein, whose pathological aggregation is implicated in neurodegenerative disorders, is not well understood. Establishing a phase diagram that delineates the boundaries of phase co-existence is key to understanding whether LLPS is an equilibrium or intermediate state. We demonstrate that tau and RNA reversibly form complex coacervates. While the equilibrium phase diagram can be fit to an analytical theory, a more advanced model is investigated through field theoretic simulations (FTS) that provided direct insight into the thermodynamic driving forces of tau LLPS. Together, experiment and simulation reveal that tau-RNA LLPS is stable within a narrow equilibrium window near physiological conditions over experimentally tunable parameters including temperature, salt and tau concentrations, and is entropy-driven. Guided by our phase diagram, we show that tau can be driven toward LLPS under live cell coculturing conditions with rationally chosen experimental parameters. KW - tau KW - liquid-liquid phase separation KW - phase diagram KW - field-theoretic simulations KW - complex coacervation KW - Alzheimer's disease KW - tauopathies KW - protein droplet JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -