Liquid state theory study of the microstructure and phase behavior of protein condensates

Protein condensates formed by liquid-liquid phase separation of intrinsically disordered proteins or proteins with low complexity domains are found to be ubiquitous in cells. It is believed that these condensates typically are in a homogeneous isotropic liquid state. However, their internal microstructures, which presumably are sequence-dependent, are incompletely understood. Here, we use polymer integral equation theory (PRISM), which describes globally disordered structural correlations over a wide range of length scales in melts and solutions, to study the internal organization of protein condensates. Using an associating polymer/sticker-spacer minimal model, PRISM theory allows the effect of the sequence, condensate packing fraction, sticker fraction, and the strength and range of sticker-sticker interactions on microstructural correlations to be investigated. Based on computing the spinodal curve, we also study the sequence-specificity of the competition between macro- and micro-phase separation. Example calculations will be presented motivated by their direct or generic biological relevance. The structural results are also germane to constructing theories of dynamics, viscoelasticity, and kinetic arrest in condensates.