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  • Open Access

Active loop extrusion modulates the mechanical response of chromatin under tension

Hossein Salari*

Daniel Jost†

  • Laboratoire de Biologie et Modélisation de la Cellule, École Normale Supérieure de Lyon, CNRS, UMR5239, Inserm U1293, Université Claude Bernard Lyon 1, 46 Allée d’Italie, 69007 Lyon, France

  • *Contact author: hossein.salari@curie.fr
  • †Contact author: daniel.jost@ens-lyon.fr
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Phys. Rev. Research 8, 013188 – Published 20 February, 2026

DOI: https://doi.org/10.1103/qfdv-vhv1

Abstract

Chromosomes are complex biopolymers folded into dynamic loops via a loop-extrusion process and may experience various mechanical forces in vivo. We develop a force-dependent model of chromatin loop extrusion and investigate its mechanical consequences on chromosome organization using simulations and analytical theory. We show that loop extrusion alters the force-extension behavior of DNA in a nonmonotonic manner: Extrusion stiffens the chain at low forces but softens it at intermediate and high forces. Our model predicts hysteresis in pulling-recoiling cycles and out-of-equilibrium responses, qualitatively consistent with recent single-chromosome stretching experiments. We further find that loop extrusion provides mechanical robustness to chromatin by promoting compaction while enabling rapid structural recovery after stress. These results establish loop extrusion as a key regulator of chromatin mechanics.

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References (30)

  1. J. Zuin, G. Roth, Y. Zhan, J. Cramard, J. Redolfi, E. Piskadlo, P. Mach, M. Kryzhanovska, G. Tihanyi, H. Kohler et al., Nonlinear control of transcription through enhancer–promoter interactions, Nature (London) 604, 571 (2022).
  2. D. J. Emerson, P. A. Zhao, A. L. Cook, R. J. Barnett, K. N. Klein, D. Saulebekova, C. Ge, L. Zhou, Z. Simandi, M. K. Minsk et al., Cohesin-mediated loop anchors confine the locations of human replication origins, Nature (London) 606, 812 (2022).
  3. A. Piazza, H. Bordelet, A. Dumont, A. Thierry, J. Savocco, F. Girard, and R. Koszul, Cohesin regulates homology search during recombinational DNA repair, Nat. Cell Biol. 23, 1176 (2021).
  4. C. Arnould, V. Rocher, F. Saur, A. S. Bader, F. Muzzopappa, S. Collins, E. Lesage, B. Le Bozec, N. Puget, T. Clouaire et al., Chromatin compartmentalization regulates the response to DNA damage, Nature (London) 623, 183 (2023).
  5. B. Akiyoshi, K. K. Sarangapani, A. F. Powers, C. R. Nelson, S. L. Reichow, H. Arellano-Santoyo, T. Gonen, J. A. Ranish, C. L. Asbury, and S. Biggins, Tension directly stabilizes reconstituted kinetochore-microtubule attachments, Nature (London) 468, 576 (2010).
  6. Y. Kalukula, A. D. Stephens, J. Lammerding, and S. Gabriele, Mechanics and functional consequences of nuclear deformations, Nat. Rev. Mol. Cell Biol. 23, 583 (2022).
  7. B. Maier, D. Bensimon, and V. Croquette, Replication by a single DNA polymerase of a stretched single-stranded DNA, Proc. Natl. Acad. Sci. USA 97, 12002 (2000).
  8. H. Yin, M. D. Wang, K. Svoboda, R. Landick, S. M. Block, and J. Gelles, Transcription against an applied force, Science 270, 1653 (1995).
  9. D. Saintillan, M. J. Shelley, and A. Zidovska, Extensile motor activity drives coherent motions in a model of interphase chromatin, Proc. Natl. Acad. Sci. USA 115, 11442 (2018).
  10. C. Dekker, C. H. Haering, J.-M. Peters, and B. D. Rowland, How do molecular motors fold the genome?, Science 382, 646 (2023).
  11. S. S. Rao, S.-C. Huang, B.G. St Hilaire, J. M. Engreitz, E. M. Perez, K.-R. Kieffer-Kwon, A. L. Sanborn, S. E. Johnstone, G. D. Bascom, I. D. Bochkov et al., Cohesin loss eliminates all loop domains, Cell 171, 305 (2017).
  12. M. Gabriele, H.B. Brandão, S. Grosse-Holz, A. Jha, G.M. Dailey, C. Cattoglio, T.-H.S. Hsieh, L. Mirny, C. Zechner, and A.S. Hansen, Dynamics of CTCF- and cohesin-mediated chromatin looping revealed by live-cell imaging, Science 376, 496 (2022).
  13. I. F. Davidson, B. Bauer, D. Goetz, W. Tang, G. Wutz, and J.-M. Peters, DNA loop extrusion by human cohesin, Science 366, 1338 (2019).
  14. M. Ganji, I. A. Shaltiel, S. Bisht, E. Kim, A. Kalichava, C. H. Haering, and C. Dekker, Real-time imaging of DNA loop extrusion by condensin, Science 360, 102 (2018).
  15. F. Conforto, Y. Gutierrez Fosado, and D. Michieletto, Fluidification of entangled polymers by loop extrusion, Phys. Rev. Res. 6, 033160 (2024).
  16. D. Breoni, C. Kurzthaler, B. Liebchen, H. Löwen, and S. Mandal, Giant activity-induced elasticity in entangled polymer solutions, Nat. Commun. 16, 5305 (2025).
  17. C. F. Nielsen, H. Witt, A. Ridolfi, B. Kempers, E. M. Chameau, S. van der Smagt, M. Barisic, E. J. Peterman, G. J. Wuite, and I. D. Hickson, Condensin I confers stiffness and centromeric cohesion to mitotic chromosomes, bioRxiv. https://www.biorxiv.org/content/10.1101/2025.04.29.651176v1
  18. V.I. Keizer, S. Grosse-Holz, M. Woringer, L. Zambon, K. Aizel, M. Bongaerts, F. Delille, L. Kolar-Znika, V.F. Scolari, S. Hoffmann et al., Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics, Science 377, 489 (2022).
  19. A. E. Meijering, K. Sarlos, C. F. Nielsen, H. Witt, J. Harju, E. Kerklingh, G. H. Haasnoot, A. H. Bizard, I. Heller, C. P. Broedersz et al., Nonlinear mechanics of human mitotic chromosomes, Nature (London) 605, 545 (2022).
  20. See Supplemental Material at http://link.aps.org/supplemental/10.1103/qfdv-vhv1 for additional method and figures.
  21. H. Salari, M. Di Stefano, and D. Jost, Spatial organization of chromosomes leads to heterogeneous chromatin motion and drives the liquid- or gel-like dynamical behavior of chromatin, Genome Res. 32, 28 (2022).
  22. H. Salari, G. Fourel, and D. Jost, Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization, Nat. Commun. 15, 5393 (2024).
  23. G. Fudenberg, M. Imakaev, C. Lu, A. Goloborodko, N. Abdennur, and L. Mirny, Formation of chromosomal domains by loop extrusion, Cell Rep. 15, 2038 (2016).
  24. G. Pobegalov, L.-Y. Chu, J.-M. Peters, and M.I. Molodtsov, Single cohesin molecules generate force by two distinct mechanisms, Nat. Commun. 14, 3946 (2023).
  25. A. Bonato, J.-W. Jang, D.-G. Kim, K.-W. Moon, D. Michieletto, and J.-K. Ryu, Spontaneously directed loop extrusion in SMC complexes emerges from broken detailed balance and anisotropic DNA search, Nucleic Acids Res. 53, gkaf725 (2025).
  26. S. B. Smith, L. Finzi, and C. Bustamante, Direct mechanical measurements of the elasticity of single DNA molecules by using magnetic beads, Science 258, 1122 (1992).
  27. S. Cocco, J. Marko, R. Monasson, A. Sarkar, and J. Yan, Force-extension behavior of folding polymers, Eur. Phys. J. E 10, 249 (2003).
  28. P. Rissone, C. V. Bizarro, and F. Ritort, Stem–loop formation drives RNA folding in mechanical unzipping experiments, Proc. Natl. Acad. Sci. USA 119, e2025575119 (2022).
  29. K. Samejima, J. H. Gibcus, S. Abraham, F. Cisneros-Soberanis, I. Samejima, A. J. Beckett, N. Pučeková, M. A. Abad, C. Spanos, B. Medina-Pritchard et al., Rules of engagement for condensins and cohesins guide mitotic chromosome formation, Science 388, eadq1709 (2025).
  30. https://github.com/physical-biology-of-chromatin/ForceExtensionLoopExtrusion.

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Phys. Rev. Research 8, 013188– Published 20 February, 2026
  • Received 16 September 2025
  • Accepted 14 November 2025
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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