title: Emergence of homeostatic epithelial packing and stress dissipation through divisions oriented along the long cell axis.
abstract: Cell division plays an important role in animal tissue morphogenesis, which depends, critically, on the orientation of divisions. In isolated adherent cells, the orientation of mitotic spindles is sensitive to interphase cell shape and the direction of extrinsic mechanical forces. In epithelia, the relative importance of these two factors is challenging to assess. To do this, we used suspended monolayers devoid of ECM, where divisions become oriented following a stretch, allowing the regulation and function of epithelial division orientation in stress relaxation to be characterized. Using this system, we found that divisions align better with the long, interphase cell axis than with the monolayer stress axis. Nevertheless, because the application of stretch induces a global realignment of interphase long axes along the direction of extension, this is sufficient to bias the orientation of divisions in the direction of stretch. Each division redistributes the mother cell mass along the axis of division. Thus, the global bias in division orientation enables cells to act collectively to redistribute mass along the axis of stretch, helping to return the monolayer to its resting state. Further, this behavior could be quantitatively reproduced using a model designed to assess the impact of autonomous changes in mitotic cell mechanics within a stretched monolayer. In summary, the propensity of cells to divide along their long axis preserves epithelial homeostasis by facilitating both stress relaxation and isotropic growth without the need for cells to read or transduce mechanical signals.
authors.affiliation: Center for Mathematics, Physics, and Engineering in the Life Sciences and Experimental Biology, Medical Research Council's Laboratory for Molecular Cell Biology, London Centre for Nanotechnology, University College London, London, WC1H 0AH, United Kingdom;
authors.forename: Tom P J
authors.initials: TP
authors.lastname: Wyatt
authors.affiliation: London Centre for Nanotechnology, University College London, London, WC1H 0AH, United Kingdom; Bioengineering, University of California, Berkeley, CA 94720;
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Harris
authors.affiliation: Medical Research Council's Laboratory for Molecular Cell Biology.
authors.forename: Maxine
authors.initials: M
authors.lastname: Lam
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, United Kingdom; and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Medical Research Council's Laboratory for Molecular Cell Biology, Centre de Recherche de Biochimie Macromoléculaire, 34293 Montpellier, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Bellis
authors.affiliation: Center for Mathematics, Physics, and Engineering in the Life Sciences and Experimental Biology, Medical Research Council's Laboratory for Molecular Cell Biology.
authors.forename: Andrea
authors.initials: A
authors.lastname: Dimitracopoulos
authors.affiliation: Department of Engineering, University of Cambridge, Cambridge CB2 1PZ, United Kingdom; and.
authors.forename: Alexandre J
authors.initials: AJ
authors.lastname: Kabla
authors.affiliation: London Centre for Nanotechnology, University College London, London, WC1H 0AH, United Kingdom; Department of Cell and Developmental Biology, and Institute for the Physics of Living Systems, University College London, London WC1E 6BT, United Kingdom; g.charras@ucl.ac.uk b.baum@ucl.ac.uk.
authors.forename: Guillaume T
authors.initials: GT
authors.lastname: Charras
authors.affiliation: Medical Research Council's Laboratory for Molecular Cell Biology, Institute for the Physics of Living Systems, University College London, London WC1E 6BT, United Kingdom; g.charras@ucl.ac.uk b.baum@ucl.ac.uk.
authors.forename: Buzz
authors.initials: B
authors.lastname: Baum
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002455:Cell Division; D048430:Cell Shape; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology*; D004848:Epithelium / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006706:Homeostasis; D061985:Madin Darby Canine Kidney Cells; D008938:Mitosis; D009024:Morphogenesis; D012984:Software; D013314:Stress, Mechanical
chemical_list: D015820:Cadherins; D049452:Green Fluorescent Proteins
keywords: cell division; mechanical feedback; mitotic rounding; morphogenesis; quantitative biology