title: Homogenizing cellular tension by hepatocyte growth factor in expanding epithelial monolayer.
abstract: Hepatocyte growth factor (HGF) induces cell migration and scattering by mechanisms that are thought to tip a local balance of competing physical forces; cell-to-cell and cell-to-substrate forces. In this local process, HGF is known to attenuate local cadherin-dependent adhesion forces for cell-cell junction development and enhance local integrin-dependent contractile forces for pulling neighboring cells apart. Here we use an expanding island of confluent Madin-Darby canine kidney (MDCK) cells as a model system to quantify the collective cell migration. In the absence of HGF, cell trajectories are highly tortuous whereas in the presence of HGF, they become far less so, resembling free expansion of a gas. At the level of cell-to-cell junctions, HGF attenuates the linkage of stress fibers to cell-to-cell junctions with concomitant decrease in intercellular stress. At the level of cell-to-substrate junctions, HGF augments the linkage of stress fibers to cell-to-substrate junctions with no apparent effect on traction. Together, HGF induces both structural changes in the actin-bound junctional protein complex and physical forces spanning multicellular clusters, which further promotes the expansion of confluent cellular layer.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.
authors.forename: Hwanseok
authors.initials: H
authors.lastname: Jang
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.|Department of Engineering Physics, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Notbohm
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.|Department of Biomedical Engineering, Hanyang University, Seoul 04763, Korea.
authors.forename: Bomi
authors.initials: B
authors.lastname: Gweon
authors.affiliation: Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Youngbin
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, Korea University, Seoul 02841, Korea.
authors.forename: Sun-Ho
authors.initials: SH
authors.lastname: Kee
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Fredberg
authors.affiliation: Department of Mechanical Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea.
authors.forename: Jennifer H
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.
authors.forename: Yongdoo
authors.initials: Y
authors.lastname: Park
mesh_terms: D000199:Actins / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D015820:Cadherins / Q000737:chemistry / Q000235:genetics*; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000737:chemistry / Q000235:genetics*; D016023:Integrins / Q000737:chemistry / Q000235:genetics; D007365:Intercellular Junctions / Q000235:genetics; D061985:Madin Darby Canine Kidney Cells; D046912:Multiprotein Complexes / Q000737:chemistry / Q000235:genetics*; D011485:Protein Binding / Q000235:genetics
chemical_list: D000199:Actins; D015820:Cadherins; D016023:Integrins; D046912:Multiprotein Complexes; D017228:Hepatocyte Growth Factor