title: Mapping the dynamics of force transduction at cell-cell junctions of epithelial clusters.
abstract: Force transduction at cell–cell adhesions regulates tissue development, maintenance and adaptation. We developed computational and experimental approaches to quantify, with both sub-cellular and multi-cellular resolution, the dynamics of force transmission in cell clusters. Applying this technology to spontaneously-forming adherent epithelial cell clusters, we found that basal force fluctuations were coupled to E-cadherin localization at the level of individual cell–cell junctions. At the multi-cellular scale, cell–cell force exchange depended on the cell position within a cluster, and was adaptive to reconfigurations due to cell divisions or positional rearrangements. Importantly, force transmission through a cell required coordinated modulation of cell-matrix adhesion and actomyosin contractility in the cell and its neighbors. These data provide insights into mechanisms that could control mechanical stress homeostasis in dynamic epithelial tissues, and highlight our methods as a resource for the study of mechanotransduction in cell–cell adhesions [corrected].
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Mei Rosa
authors.initials: MR
authors.lastname: Ng
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Achim
authors.initials: A
authors.lastname: Besser
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Joan S
authors.initials: JS
authors.lastname: Brugge
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, United States.
authors.forename: Gaudenz
authors.initials: G
authors.lastname: Danuser
mesh_terms: D000205:Actomyosin / Q000235:genetics / Q000378:metabolism; D022005:Adherens Junctions / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D021982:Cell-Matrix Junctions / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D015870:Gene Expression; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D013314:Stress, Mechanical
chemical_list: D015820:Cadherins; D000205:Actomyosin
keywords: cell adhesion; cell biology; cell–cell interactions; cell–matrix interactions; intercellular adhesion molecules; mechanical forces; mechanotransduction; none