title: Substrate stiffness regulates cadherin-dependent collective migration through myosin-II contractility.
abstract: The mechanical microenvironment is known to influence single-cell migration; however, the extent to which mechanical cues affect collective migration of adherent cells is not well understood. We measured the effects of varying substrate compliance on individual cell migratory properties in an epithelial wound-healing assay. Increasing substrate stiffness increased collective cell migration speed, persistence, and directionality as well as the coordination of cell movements. Dynamic analysis revealed that wounding initiated a wave of motion coordination from the wound edge into the sheet. This was accompanied by a front-to-back gradient of myosin-II activation and establishment of cell polarity. The propagation was faster and farther reaching on stiff substrates, indicating that substrate stiffness affects the transmission of directional cues. Manipulation of myosin-II activity and cadherin-catenin complexes revealed that this transmission is mediated by coupling of contractile forces between neighboring cells. Thus, our findings suggest that the mechanical environment integrates in a feedback with cell contractility and cell-cell adhesion to regulate collective migration.
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mei Rosa
authors.initials: MR
authors.lastname: Ng
authors.forename: Achim
authors.initials: A
authors.lastname: Besser
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry / Q000378:metabolism*; D015153:Blotting, Western; D001940:Breast / Q000166:cytology / Q000378:metabolism*; D015820:Cadherins / Q000494:pharmacology*; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D059008:Time-Lapse Imaging; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology; D000099166:Polyacrylamides
chemical_list: D000180:Acrylic Resins; D015820:Cadherins; D051177:Catenins; D006576:Heterocyclic Compounds, 4 or More Rings; D024462:Myosin Type II; D012333:RNA, Messenger; D000099166:Polyacrylamides; C472645:blebbistatin