Interplay of Structural Heterogeneity and Active Remodeling Controls Chromatin Condensate Organization and Dynamics
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Chromatin is an actively remodeled polymeric system whose organization emerges from the interplay of equilibrium interactions and ATP-dependent processes. Recent in vitro experiments show that nucleosome spacing and ATP-dependent remodeler activity significantly influence chromatin condensate properties. Here, guided by these observations, we develop a hierarchy of coarse-grained models that systematically dissect the roles of nucleosome spacing, remodeler-mediated binding–unbinding, and active force generation in governing condensate dynamics. We demonstrate that nucleosome spacing heterogeneity is a key determinant of condensate material properties. Condensates formed from regularly spaced fibers exhibit enhanced internal mixing, whereas those assembled from disordered spacing develop pronounced structural correlations, increased entanglement, and suppressed internal dynamics. Incorporating remodeler-like binding–unbinding non-equilibrium kinetics drives local structural reorganization, leading to condensate swelling and a substantial acceleration of internal relaxation. In a condensate of heterogeneous fibers, contrasts in spacing and activity robustly drive spatial segregation, giving rise to stable core–shell architectures. Strikingly, when dipolar forces are coupled to hydrodynamic interactions, serving as a minimal representation of active nucleosome translocation, condensates exhibit enhanced center-of-mass motion. Together, our results establish a predictive coarse-grained framework that quantitatively links structural heterogeneity and active processes to emergent chromatin-like condensate organization, mechanics, and transport.
Chromatin forms dynamic condensates in living cells that play important roles in genome organization and regulation. Recent in vitro experiments have shown that condensate properties are strongly influenced by the arrangement of nucleosomes, the protein complexes around which DNA is wrapped, along chromatin fibers and by ATP-dependent remodeling activity. However, the mechanisms linking these molecular processes to condensate behavior remain poorly understood. Using a hierarchy of coarse-grained models, we identify the distinct roles of structural heterogeneity, remodeler-mediated kinetics, and active force generation in chromatin condensates. By providing a mechanistic explanation for experimental observations, our work establishes a physical framework connecting chromatin architecture and energy-consuming processes to condensate organization, dynamics, and function.
