Regulating and targeting liquid phase separation

Three modes of action currently link phase separation to pathology with the potential to serve as pathways for intervention. (A) The phase boundary, a metric for the propensity to phase-separate, is defined by the saturation concentration and the relative interaction strengths between molecules. (B) Material properties of condensed phases include viscoelasticity, reversibility of exchange, and the dynamics and mobility of molecules within and across droplets. (C) Fiber formation may be nucleated within droplets, potentially giving rise to pathology. These three modes of action, which are sensitive to disease-associated conditions, highlight distinct avenues for regulation and therapeutic targeting of liquid phase separation in disease. (Reproduced with author permission from: Elbaum-Garfinkle, S. Matter over mind: Liquid phase separation and neurodegeneration. J Biol Chem 2019;294(18):7160-68.)