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.
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•HP1α (Swi6) is critical for nuclear resistance to external force•H3K9me2/3 and chromatin-bound Swi6 are insufficient to promote nuclear stiffness•The contribution of Swi6 to nuclear mechanics requires its ability to undergo condensation•100-nm-scale biomolecular condensates can affect micrometer-scale organelle mechanics
In this work, Williams et al. reveal a mechanical role for biomolecular condensation in supporting nuclear mechanics through genetic dissection of the mechanisms by which heterochromatin protein HP1α (Swi6) influences nuclear stiffness.