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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. 

Abstract In the last decade, organ-on-a-chip technology has been researched as an alternative to animal and cell culture models (Buhidma et al. in NPJ Parkinson’s Dis, 2020; Pearce et al. in Eur Cells Mater 13:1–10, 2007; Huh et al. in Nat Protoc 8:2135–2157, 2013). While extensive research has focused on the biological functions of these chips, there has been limited exploration of functional materials that can accurately replicate the biological environment. Our group concentrated on a lung-on-a-chip featuring a newly fabricated porous silicon bio-membrane. This bio-membrane mimics the interstitial space found between epithelial and endothelial cells in vivo, with a thickness of approximately 1 μm (Ingber in Cell 164:1105–1109, 2016). This study aims to establish a fabrication method for producing a thin, uniform porous silicon membrane with a predictablereduced modulus. We conducted mechanical and morphological characterization using scanning electron microscopy and nanoindentation. A small, parametric study was conducted to determine the reduced modulus of the porous silicon and how it may relate to the morphological features of the membrane. We compare our results to other works. Graphical Abstract