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

TL;DR

This study uses simulations to explore how proteins and chromatin interact to form various phase-separated condensates, revealing new regimes where chromatin influences droplet formation and dynamics, relevant to cellular biology.

Contribution

It introduces a simulation framework for protein-chromatin interactions, identifying novel phase regimes and mechanisms of condensate formation not previously characterized.

Findings

Protein droplets can form solely due to chromatin interactions.

Droplet density varies with protein concentration in certain regimes.

Chromatin absorption slows protein dynamics within droplets.

Abstract

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 which arise due to liquid-liquid phase separation, or a via a 'bridging-induced attraction' mechanism. For proteins which 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. Together this provides biologically relevant insights into the nature of protein-chromatin condensates in living cells.