The ripening dynamics of nuclear biomolecular condensates*

Bio-molecular condensates are implicated in many cellular processes. Condensate growth dynamics within the complex cellular environment are therefore of great importance. Chromatin mechanics have been shown to restrict condensate coarsening in the nucleus but the role of condensate properties on these growth dynamics is not well understood. Here, we show that condensate surface tension and the interplay with chromatin mechanics govern condensate growth in the nucleus. By using a chemical dimerization approach to induce condensates with different proteins in live cell nuclei, we found that one grew mainly through diffusion while the other grew mainly by ripening. To explain these distinct growth patterns, we developed a quantitative physical model that assessed nuclear condensate growth as diffusion-based growth in an elastic mesh network, where the condensates experience size dependent pressure from the chromatin. Our model reveals that alongside local chromatin stiffness gradients, the condensate surface tension influences the ripening propensity of condensates and can explain the experimental growth patterns. By matching the experimentally observed ripening patterns with model predictions, we reveal that the condensate with greater surface tension undergoes Ostwald ripening while the condensate with lower surface tension experiences suppressed Ostwald ripening and occasionally, Elastic ripening. The model can also explain the difference in the growth exponent for the two condensates and predicts that the growth of high surface tension condensate would be less sensitive to changes in chromatin environment, which is confirmed by experiment. Through combination of theory and experiments, our work reveals that nuclear condensate surface tension can be high enough to compete with chromatin stiffness to govern condensate growth dynamics, which sheds light on how cells can regulate condensate properties and chromatin stiffness together to control condensate stability and sizes in the nucleus.