Abstract:
Biomolecular condensates have emerged as major drivers of cellular organization. It remains largely unexplored, however, whether these condensates can impart mechanical function(s) to the cell. The heterochromatin protein HP1α (Swi6 in Schizosaccharomyces pombe) crosslinks histone H3K9 methylated nucleosomes and has been proposed to undergo condensation to drive the liquid-like clustering of heterochromatin domains. Here, we leverage the genetically tractable S. pombe model and a separation-of-function allele to elucidate a mechanical function imparted by Swi6 condensation. Using single-molecule imaging, force spectroscopy, and high-resolution live-cell imaging, we show that Swi6 is critical for nuclear resistance to external force. Strikingly, it is the condensed yet dynamic pool of Swi6, rather than the chromatin-bound molecules, that is essential to imparting mechanical stiffness. Our findings suggest that Swi6 condensates embedded in the chromatin meshwork establish the emergent mechanical behavior of the nucleus as a whole, revealing that biomolecular condensation can influence organelle and cell mechanics.
摘要:
生物分子缩合物已经成为细胞组织的主要驱动因素。它在很大程度上仍未被探索,然而,这些冷凝物是否可以赋予细胞机械功能。异染色质蛋白HP1α(裂殖酵母中的Swi6)交联组蛋白H3K9甲基化核小体,并已被提议进行缩合以驱动异染色质结构域的液状聚类。这里,我们利用可遗传处理的S.pombe模型和功能分离等位基因来阐明Swi6缩合赋予的机械功能。使用单分子成像,力光谱学,和高分辨率活细胞成像,我们证明Swi6对于核抵抗外力至关重要。引人注目的是,它是Swi6浓缩但动态的池,而不是染色质结合的分子,这对赋予机械刚度至关重要。我们的发现表明,嵌入染色质网中的Swi6凝聚物建立了整个细胞核的新兴机械行为,揭示了生物分子缩合可以影响细胞器和细胞力学。