The condensation of HP1α/Swi6 imparts nuclear stiffness
Jessica F. Williams,
Ivan V. Surovtsev,
Sarah M. Schreiner,
Ziyuan Chen,
Gulzhan Raiymbek,
Hang Nguyen,
Yan Hu,
Julie S. Biteen,
Simon G.J. Mochrie,
Kaushik Ragunathan,
Megan C. King
Affiliations
Jessica F. Williams
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Ivan V. Surovtsev
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Physics, Yale University, 217 Prospect Street, New Haven, CT 06511, USA
Sarah M. Schreiner
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Ziyuan Chen
Department of Biophysics, University of Michigan, Ann Arbor, MI 48109, USA
Gulzhan Raiymbek
Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Hang Nguyen
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Yan Hu
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA
Julie S. Biteen
Department of Biophysics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA
Simon G.J. Mochrie
Department of Physics, Yale University, 217 Prospect Street, New Haven, CT 06511, USA
Kaushik Ragunathan
Department of Biology, Brandeis University, Waltham, MA 02453, USA; Corresponding author
Megan C. King
Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Corresponding author
Summary: 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.
