Simulating the chromatin-mediated phase separation of model proteins with multiple domains

We perform simulations of a system containing simple model proteins and a polymer representing chromatin. We study the interplay between protein-protein and protein-chromatin interactions, and the resulting condensates that arise due to liquid-liquid phase separation, or a via a “bridging-induced attraction” mechanism. For proteins that interact multivalently, we obtain a phase diagram which includes liquid-like droplets, droplets with absorbed polymer, and coated polymer regimes. Of particular interest is a regime where protein droplets only form due to interaction with the polymer; here, unlike a standard phase separating system, droplet density rather than size varies with the overall protein concentration. We also observe that protein dynamics within droplets slow down as chromatin is absorbed. If the protein-protein interactions have a strictly limited valence, fractal or gel-like condensates are instead observed. A specific example that inspired our model is heterochromatin protein 1, or HP1. Recent in vivo experiments have shown that HP1 exhibits similar droplet size buffering behavior as our simulations. Overall, our results provide biologically relevant insights into the general nature of protein-chromatin condensates in living cells.