Interplay of condensate material properties and chromatin heterogeneity governs nuclear condensate ripening

Abstract

Nuclear condensates play many important roles in chromatin functions, but how cells regulate their nucleation and growth within the complex nuclear environment is not well understood. Here, we report how condensate properties and chromatin mechanics dictate condensate growth dynamics in the nucleus. We induced condensates with distinct properties using different proteins in human cell nuclei and monitored their growth. We revealed two key physical mechanisms that underlie droplet growth: diffusion-driven or ripening-dominated growth. To explain the experimental observations, we developed a quantitative theory that uncovers the mechanical role of chromatin and condensate material properties in regulating condensate growth in a heterogeneous environment. By fitting our theory to experimental data, we find that condensate surface tension is critical in determining whether condensates undergo elastic or Ostwald ripening. Our model also predicts that chromatin heterogeneity can influence condensate nucleation and growth, which we validated by experimentally perturbing the chromatin organization and controlling condensate nucleation. By combining quantitative experimentation with theoretical modeling, our work elucidates how condensate surface tension and chromatin heterogeneity govern nuclear condensate ripening, implying that cells can control both condensate properties and the chromatin organization to regulate condensate growth in the nucleus.