title: E-cadherin-mediated force transduction signals regulate global cell mechanics.
abstract: This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.
authors.affiliation: Department of Biochemistry, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
authors.forename: Ismaeel
authors.initials: I
authors.lastname: Muhamed
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Sehgal
authors.affiliation: Department of Biochemistry, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
authors.forename: Arash
authors.initials: A
authors.lastname: Tajik
authors.affiliation: Department of Mechanical Science and Engineering, University of Illinois Urbana Champaign, Urbana, IL 61801, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Illinois Urbana Champaign, Urbana, IL 61801, USA Department of Chemical and Biomolecular Engineering, University of Illinois Urbana Champaign, Urbana, IL 61801, USA Department of Chemistry, University of Illinois Urbana Champaign, Urbana, IL 61801, USA Carl W. Woese Institute of Genomic Biology, University of Illinois Urbana Champaign, Urbana, IL 61801, USA leckband@illinois.edu.
authors.forename: Deborah E
authors.identifier: 0000-0002-7557-766X
authors.initials: DE
authors.lastname: Leckband
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D061985:Madin Darby Canine Kidney Cells; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051178:alpha Catenin; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Cell signaling; E-cadherin; Integrin; Magnetic twisting cytometry; Mechanotransduction; Traction force microscopy