title: Activation of beta 1 but not beta 3 integrin increases cell traction forces.
abstract: Cell-generated traction forces induce integrin activation, leading to focal adhesion growth and cell spreading. It remains unknown, however, whether integrin activation feeds back to impact the generation of cytoskeletal tension. Here, we used elastomeric micropost arrays to measure cellular traction forces in wildtype and integrin-null cells. We report that activation of β1 but not β3 integrin, by either increasing density of immobilized fibronectin or treating with manganese, elicited fibroblast spreading and cytoskeletal tension. Furthermore, this force generation required Rho kinase and myosin activity. These findings suggest that integrin activation and cell traction forces comprise a bi-directional signaling unit of cell adhesion.
authors: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA. grlin@mail.med.upenn.edu
authors: Grace L
authors: GL
authors: Lin
authors: Daniel M
authors: DM
authors: Cohen
authors: Ravi A
authors: RA
authors: Desai
authors: Mark T
authors: MT
authors: Breckenridge
authors: Lin
authors: L
authors: Gao
authors: Martin J
authors: MJ
authors: Humphries
authors: Christopher S
authors: CS
authors: Chen
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005353:Fibronectins / Q000737:chemistry; D055767:Immobilized Proteins / Q000737:chemistry; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051379:Mice; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013500:Surface Tension; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D005353:Fibronectins; D055767:Immobilized Proteins; D039482:Integrin alpha5; D019012:Integrin beta1; D039661:Integrin beta3; D034741:RNA, Small Interfering; D008345:Manganese; D054460:rho-Associated Kinases; D009218:Myosins
references: Tissue Eng. 2004 May-Jun;10(5-6):865-72
references: 15265304
references: EMBO Rep. 2011 Mar;12(3):259-66
references: 21311561
references: J Clin Invest. 1999 Jan;103(2):229-38
references: 9916135
references: J Cell Biol. 2005 May 9;169(3):515-26
references: 15866889
references: Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1484-9
references: 12552122
references: J Biol Chem. 1998 May 1;273(18):10988-93
references: 9556578
references: Science. 2002 Apr 5;296(5565):151-5
references: 11884718
references: J Cell Sci. 1988 Apr;89 ( Pt 4):507-13
references: 3198704
references: Mol Biol Cell. 2004 Jun;15(6):2943-53
references: 15075376
references: J Cell Biol. 2002 Dec 9;159(5):881-91
references: 12473693
references: Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9051-5
references: 7692444
references: Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16245-50
references: 19805288
references: Curr Biol. 2006 Feb 7;16(3):242-51
references: 16461277
references: Science. 2009 Jan 30;323(5914):642-4
references: 19179533
references: J Mol Cell Cardiol. 2011 Jan;50(1):203-13
references: 20937283
references: Biophys J. 2010 Feb 17;98(4):543-51
references: 20159150
references: Biophys J. 2007 Apr 15;92(8):2964-74
references: 17277192
references: EMBO J. 2011 Nov 16;30(22):4539-53
references: 21926969
references: Dev Cell. 2004 Apr;6(4):483-95
references: 15068789
references: J Cell Biol. 1996 Jun;133(6):1403-15
references: 8682874
references: Curr Opin Cell Biol. 1998 Oct;10(5):566-71
references: 9818165
references: J Biol Chem. 1995 Oct 27;270(43):25570-7
references: 7592728
references: Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2048-53
references: 10051592
references: Annu Rev Cell Dev Biol. 2011;27:321-45
references: 21663444
references: J Cell Sci. 2008 Feb 1;121(Pt 3):265-71
references: 18216331
references: J Cell Biol. 2010 Mar 22;188(6):877-90
references: 20308429
references: Curr Opin Genet Dev. 2001 Feb;11(1):48-53
references: 11163150
references: J Cell Biol. 2005 Oct 24;171(2):383-92
references: 16247034
references: Cell. 1996 Feb 9;84(3):371-9
references: 8608590
references: J Biol Chem. 1998 Dec 25;273(52):34710-5
references: 9856993
references: J Cell Sci. 2006 Oct 1;119(Pt 19):3901-3
references: 16988024
references: J Cell Sci. 1999 Aug;112 ( Pt 16):2677-91
references: 10413676
references: Exp Cell Res. 2007 Oct 1;313(16):3616-23
references: 17673200
references: Integr Biol (Camb). 2011 Jun;3(6):663-74
references: 21445393
references: Exp Cell Res. 2007 Jan 1;313(1):22-37
references: 17081517
references: Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):
references: 21421922
references: Gastroenterology. 2012 Apr;142(4):928-937.e3
references: 22202457
references: Nat Methods. 2010 Sep;7(9):733-6
references: 20676108
references: J Cell Sci. 2009 Nov 15;122(Pt 22):4009-11
references: 19910492
references: J Biol Chem. 2001 Jul 13;276(28):26448-52
references: 11340081
references: J Cell Sci. 1998 Jun;111 ( Pt 11):1535-44
references: 9580561