Intermolecular interaction and local chromatin density regulate biomolecular condensate growth inside the nucleus

Biomolecular condensates play important functional roles in many cellular processes. How the complex mechanical environment of the cell affects the growth of biomolecular condensates is not well understood. We study the growth of biomolecular condensates embedded in the chromatin network inside the nucleus. Chemical dimerization tools were used to induce protein condensates and their growth dynamics was observed for many hours. We combine theoretical modelling and experiments to characterize the growth dynamics of the condensates (droplets). We uncover the criteria for ripening-suppressed droplet growth and growth via ripening, depending on local chromatin stiffness, and demonstrate that these two distinct droplet dynamics may coexist within the complex mechanical environment inside the nucleus. Our theoretical predictions and experimental quantifications show that depending on the properties of the droplet forming protein and the mechanical properties of the chromatin network, the droplets can be stable or undergo ripening. Our overall findings point towards a possible repertoire of control mechanisms the cell can employ to regulate many aspects of the biomolecular condensate growth dynamics inside the nucleus.