关键词: Biomolecular condensates Chromatin Elastic ripening Nuclear bodies Ostwald ripening

来  源:   DOI:10.1101/2024.05.07.593010   PDF(Pubmed)

Abstract:
Biomolecular condensates play pivotal roles in many cellular processes, yet predicting condensate growth dynamics within the complex intracellular environment is challenging. While chromatin mechanics are known to influence condensate coarsening in the nucleus, the effect of condensate properties remains unclear. Our study demonstrates that the interplay between condensate properties and chromatin mechanics dictates condensate growth dynamics. Through chemical dimerization, we induced condensates of various properties in the cell nuclei, revealing distinct growth mechanisms: diffusion-driven or ripening-dominated. To explain experimental observations, we developed a quantitative theory that uncovers the role of chromatin in modulating condensate growth via size-dependent pressure. We find that surface tension is a critical factor in determining whether condensates undergo elastic or Ostwald ripening. Our model predicts that different condensates are affected differently by chromatin heterogeneity, validated by experimentally perturbing chromatin organization. Taken together, our work elucidates how condensate surface tension and chromatin heterogeneity govern nuclear condensate ripening.
摘要:
生物分子缩合物在许多细胞过程中起着关键作用,然而,预测复杂的细胞内环境中的冷凝物生长动力学是具有挑战性的。虽然已知染色质力学会影响细胞核中的冷凝物粗化,凝析油性质的影响尚不清楚。我们的研究表明,冷凝物性质和染色质力学之间的相互作用决定了冷凝物的生长动力学。通过化学二聚化,我们在细胞核中诱导了各种性质的凝聚物,揭示了不同的生长机制:扩散驱动或成熟主导。为了解释实验观察,我们开发了一种定量理论,揭示了染色质通过大小依赖性压力调节冷凝物生长的作用。我们发现表面张力是决定冷凝物是否经历弹性或奥斯特瓦尔德熟化的关键因素。我们的模型预测,不同的缩合物受染色质异质性的影响不同,通过实验扰动染色质组织验证。一起来看,我们的工作阐明了凝聚物表面张力和染色质异质性如何控制核凝聚物的成熟。
公众号