title: Cellular Contraction and Polarization Drive Collective Cellular Motion.
abstract: Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity.
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Engineering Physics, University of Wisconsin-Madison, Madison, Wisconsin.
authors.forename: Jacob
authors.initials: J
authors.lastname: Notbohm
authors.affiliation: James Franck Institute, The University of Chicago, Chicago, Illinois.
authors.forename: Shiladitya
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Physics and Syracuse Biomaterials Institute, Syracuse University, Syracuse, New York.
authors.forename: Kazage J C
authors.initials: KJC
authors.lastname: Utuje
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Biomedical Engineering, Hanyang University, Seoul, Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Gweon
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul, Korea.
authors.forename: Hwanseok
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Biomedical Engineering, Korea University, Seoul, Korea.
authors.forename: Yongdoo
authors.initials: Y
authors.lastname: Park
authors.affiliation: Department of Mechanical Engineering, KAIST, Daejeon, Korea.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shin
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts; Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: James P
authors.initials: JP
authors.lastname: Butler
authors.affiliation: Harvard T. H. Chan School of Public Health, Boston, Massachusetts. Electronic address: jfredber@hsph.harvard.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.affiliation: Department of Physics and Syracuse Biomaterials Institute, Syracuse University, Syracuse, New York. Electronic address: mcmarche@syr.edu.
authors.forename: M Cristina
authors.initials: MC
authors.lastname: Marchetti
mesh_terms: D000180:Acrylic Resins; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002452:Cell Count; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size; D024042:Collagen Type I / Q000378:metabolism; D004285:Dogs; D055119:Elastic Modulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009570:Nitriles / Q000494:pharmacology; D010507:Periodicity; D013499:Surface Properties
chemical_list: D000180:Acrylic Resins; D002070:Butadienes; D024042:Collagen Type I; D004791:Enzyme Inhibitors; D006576:Heterocyclic Compounds, 4 or More Rings; D009570:Nitriles; C113580:U 0126; C016680:polyacrylamide gels; D049452:Green Fluorescent Proteins; C472645:blebbistatin; D004815:Epidermal Growth Factor