Liquid state theory of microstructure and local clustering of biomolecular condensates and its consequences on slow dynamics

Biomolecular condensates formed through phase separation of proteins and nucleic acids are ubiquitous, which provide a fundamental way to organize the intracellular material in a membrane-less manner. It is believed that these condensates are typically in a homogeneous isotropic liquid state. However, their internal microstructures are incompletely understood. Here, we use the Polymer Reference Interaction Site Model liquid state integral equation theory that is highly developed for synthetic homopolymer and copolymer melts and solutions to study biomolecular condensates of periodic and aperiodic sequences in polymeric microemulsion-like states of organization. An associating polymer/sticker-spacer minimal model is employed to establish the effect of polymer packing fraction, sequence, and the strength and range of intermolecular attractions on the internal organization of condensates from the local to the microdomain/macromolecular length scale in real and Fourier space. The structural results are used as input in microscopic dynamical approaches to address the slowing down of diffusion due to clustering and physical bond formation including possible kinetic arrest into structured physical gels.