title: The tethering of chromatin to the nuclear envelope supports nuclear mechanics.
abstract: The nuclear lamina is thought to be the primary mechanical defence of the nucleus. However, the lamina is integrated within a network of lipids, proteins and chromatin; the interdependence of this network poses a challenge to defining the individual mechanical contributions of these components. Here, we isolate the role of chromatin in nuclear mechanics by using a system lacking lamins. Using novel imaging analyses, we observe that untethering chromatin from the inner nuclear membrane results in highly deformable nuclei in vivo, particularly in response to cytoskeletal forces. Using optical tweezers, we find that isolated nuclei lacking inner nuclear membrane tethers are less stiff than wild-type nuclei and exhibit increased chromatin flow, particularly in frequency ranges that recapitulate the kinetics of cytoskeletal dynamics. We suggest that modulating chromatin flow can define both transient and long-lived changes in nuclear shape that are biologically important and may be altered in disease.
authors.affiliation: Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8002, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Schreiner
authors.affiliation: Department of Physics, Yale University, 217 Prospect Street, New Haven, Connecticut 06511, USA.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Koo
authors.affiliation: Department of Applied Physics, Yale University, 15 Prospect Street, New Haven, Connecticut 06511, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 1] Department of Physics, Yale University, 217 Prospect Street, New Haven, Connecticut 06511, USA [2] Department of Applied Physics, Yale University, 15 Prospect Street, New Haven, Connecticut 06511, USA.
authors.forename: Simon G J
authors.initials: SG
authors.lastname: Mochrie
authors.affiliation: Department of Cell Biology, Yale School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520-8002, USA.
authors.forename: Megan C
authors.initials: MC
authors.lastname: King
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D034881:Nuclear Lamina; D052898:Optical Tweezers; D012568:Schizosaccharomyces
chemical_list: D002843:Chromatin