title: Extracellular Forces Cause the Nucleus to Deform in a Highly Controlled Anisotropic Manner.
abstract: Physical forces arising in the extra-cellular environment have a profound impact on cell fate and gene regulation; however the underlying biophysical mechanisms that control this sensitivity remain elusive. It is hypothesized that gene expression may be influenced by the physical deformation of the nucleus in response to force. Here, using 3T3s as a model, we demonstrate that extra-cellular forces cause cell nuclei to rapidly deform (<1 s) preferentially along their shorter nuclear axis, in an anisotropic manner. Nuclear anisotropy is shown to be regulated by the cytoskeleton within intact cells, with actin and microtubules resistant to orthonormal strains. Importantly, nuclear anisotropy is intrinsic, and observed in isolated nuclei. The sensitivity of this behaviour is influenced by chromatin organization and lamin-A expression. An anisotropic response to force was also highly conserved amongst an array of examined nuclei from differentiated and undifferentiated cell types. Although the functional purpose of this conserved material property remains elusive, it may provide a mechanism through which mechanical cues in the microenvironment are rapidly transmitted to the genome.
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Kristina
authors.initials: K
authors.lastname: Haase
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Joan K L
authors.initials: JK
authors.lastname: Macadangdang
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Claire H
authors.initials: CH
authors.lastname: Edrington
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Cuerrier
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.|Department of Biology, Gendron Hall, 30 Marie Curie, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hadjiantoniou
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.|Ottawa Institute of Systems Biology, Roger Guindon Hall, 451 Smyth Road, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Harden
authors.affiliation: Department of Biochemistry, Microbiology &Immunology, Roger Guindon Hall, 451 Smyth Road, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Ilona S
authors.initials: IS
authors.lastname: Skerjanc
authors.affiliation: Centre for Interdisciplinary NanoPhysics, Department of Physics, MacDonald Hall, 150 Louis Pasteur, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.|Department of Biology, Gendron Hall, 30 Marie Curie, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.|Institute for Science Society and Policy, Simard Hall, 60 University, University of Ottawa, Ottawa, ON, K1N 6N5, Canada.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Pelling
mesh_terms: D016475:3T3 Cells; D000818:Animals; D016880:Anisotropy; D002467:Cell Nucleus / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051379:Mice; D008962:Models, Theoretical; D013314:Stress, Mechanical