RNA regulates cohesiveness and porosity of a biological condensate.

Biological condensates have emerged as key elements of a biological cell function, concentrating disparate biomolecules to accomplish specific biological tasks. RNA was identified as a key ingredient of such condensates, however, its effect on the physical properties of the condensate was found to depend on the condensate's composition while its effect on the microstructure has remained elusive. Here, we characterize the physical properties and the microstructure of a protein-RNA condensate by means of large-scale coarse-grained (CG) molecular dynamics simulations. By developing a custom CG model of RNA compatible with a popular CG model of proteins, we systematically investigate the structural, thermodynamic, and kinetic properties of condensate droplets containing thousands of individual protein and RNA molecules over a range of temperatures. While we find RNA to increase the condensate's cohesiveness, its effect on the condensate's fluidity is more nuanced with longer molecules compacting the condensate and making it less fluid. We show that a biological condensate has a sponge-like morphology of interconnected channels of size that increases with temperature and decreases in the presence of RNA. Our results suggest that longer RNA form a dynamic scaffold within a condensate, regulating not only its fluidity but also permeability to intruder molecules.