Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics

Veer Keizer (1, 2, 3, 4, 5, 6) , Simon Grosse-Holz (7) , Maxime Woringer (1, 2, 4, 5, 6) , Laura Zambon (1, 2, 3, 4, 5, 6) , Koceila Aizel (2, 4, 5, 6) , Maud Bongaerts (2, 4, 5, 6) , Lorena Kolar-Znika (1, 2, 4, 5, 6) , Vittore Scolari (1, 2, 4, 5, 6) , Sebastian Hoffmann (3, 4, 5, 6) , Edward Banigan (7) , Leonid Mirny (7) , Maxime Dahan (2, 4, 5, 6) , Daniele Fachinetti (3, 4, 5, 6) , Antoine Coulon (1, 2, 4, 5, 6)

1 Dynamique du noyau [Institut Curie]
2 PCC - Laboratoire Physico-Chimie Curie [Institut Curie]
3 Biologie Cellulaire et Cancer
4 PSL - Université Paris sciences et lettres
5 Centre de recherche de l'Institut Curie [Paris]
6 SU - Sorbonne Université
7 Department of Physics [MIT Cambridge]

Our understanding of the physical principles organizing the genome in the nucleus is limited by the lack of tools to directly exert and measure forces on interphase chromosomes in vivo and probe their material nature. Here, we present a novel approach to actively manipulate a genomic locus using controlled magnetic forces inside the nucleus of a living human cell. We observe viscoelastic displacements over microns within minutes in response to near-picoNewton forces, which are well captured by a Rouse polymer model. Our results highlight the fluidity of chromatin, with a moderate contribution of the surrounding material, revealing the minor role of crosslinks and topological effects and challenging the view that interphase chromatin is a gel-like material. Our new technology opens avenues for future research, from chromosome mechanics to genome functions.

Domains: Life Sciences [q-bio]; Life Sciences [q-bio]; Cellular Biology; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biophysics; Life Sciences [q-bio]; Quantitative Methods [q-bio.QM]; Physics [physics]; Mechanics [physics]; Biomechanics [physics.med-ph]; Physics [physics]; Condensed Matter [cond-mat]; Soft Condensed Matter [cond-mat.soft]

Veer Keizer, Simon Grosse-Holz, Maxime Woringer, Laura Zambon, Koceila Aizel, et al.. Live-cell micromanipulation of a genomic locus reveals interphase chromatin mechanics. 2021. ⟨hal-03437297⟩