Phase separation in the nucleus is limited by chromatin mechanics

Liquid-liquid phase separation is a fundamental mechanism underlying biological organization. While conventional theory predicts that a single phase-separated condensate would be energetically favored, both natural and synthetic condensates in cells typically appear as multiple dispersed droplets with suppressed growth dynamics. Here, we combine coarse-grained molecular dynamics simulations and theory of liquid-liquid phase separation to show that mechanical interactions with chromatin can constrain the size of droplets in the nucleus. The "gel-like" chromatin suppresses both droplet coalescence and ripening dynamics, resulting in a reduced scaling exponent for mean droplet radius versus time. Our work highlights the impact of the local mechanical environment on biomolecular condensate formation and growth, and further elucidates the role of mechanics in fundamental biological processes taking place in the cell nucleus.