Liquid-Liquid Phase Separation by Tau-Polyanion Complex Coacervation and Its Relationship to Amyloid Fibrillization.*

Complex coacervation of intrinsically disordered proteins and RNA has shown both biological and pathological significance in the human body. We report here recent findings and characterizations of complex coacervates of RNA and tau, the primary constituent of Alzheimer neurofibrillary tangles. We first show that coacervation is sensitive to ionic strength and temperature, with a strong dependence on the Coulombic properties of the polyanion. We further look into the driving force of such coacervation via investigating phase behavior with classical complex coacervation theories. Within the phase diagram boundary, we present a concentrated, fluidic and dynamic liquid phase via characterization using state-of-the-art spectroscopic techniques. Finally, we investigate the connection between such physical specifications with the propensity of tau amyloid fibrilization.