title: Stretch-induced stress fiber remodeling and the activations of JNK and ERK depend on mechanical strain rate, but not FAK.
abstract: BACKGROUND
  Cells within tissues are subjected to mechanical forces caused by extracellular matrix deformation. Cells sense and dynamically respond to stretching of the matrix by reorienting their actin stress fibers and by activating intracellular signaling proteins, including focal adhesion kinase (FAK) and the mitogen-activated proteins kinases (MAPKs). Theoretical analyses predict that stress fibers can relax perturbations in tension depending on the rate of matrix strain. Thus, we hypothesized stress fiber organization and MAPK activities are altered to an extent dependent on stretch frequency.
  
  
  RESULTS
  Bovine aortic endothelial cells and human osteosarcoma cells expressing GFP-actin were cultured on elastic membranes and subjected to various patterns of stretch. Cyclic stretching resulted in strain rate-dependent increases in stress fiber alignment, cell retraction, and the phosphorylation of the MAPKs JNK, ERK and p38. Transient step changes in strain rate caused proportional transient changes in the levels of JNK and ERK phosphorylations without affecting stress fiber organization. Disrupting stress fiber contractile function with cytochalasin D or Y27632 decreased the levels of JNK and ERK phosphorylation. Previous studies indicate that FAK is required for stretch-induced cell alignment and MAPK activations. However, cyclic uniaxial stretching induced stress fiber alignment and the phosphorylation of JNK, ERK and p38 to comparable levels in FAK-null and FAK-expressing mouse embryonic fibroblasts.
  
  
  CONCLUSIONS
  These results indicate that cyclic stretch-induced stress fiber alignment, cell retraction, and MAPK activations occur as a consequence of perturbations in fiber strain. These findings thus shed new light into the roles of stress fiber relaxation and reorganization in maintenance of tensional homeostasis in a dynamic mechanical environment.
authors.affiliation: Department of Biomedical Engineering, Texas A&M University, College Station, Texas, United States of America.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Hsu
authors.forename: Chin-Fu
authors.initials: CF
authors.lastname: Lee
authors.forename: Andrea
authors.initials: A
authors.lastname: Locke
authors.forename: Susan Q
authors.initials: SQ
authors.lastname: Vanderzyl
authors.forename: Roland
authors.initials: R
authors.lastname: Kaunas
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D002417:Cattle; D045744:Cell Line, Tumor; D048430:Cell Shape; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D022502:Stress Fibers / Q000378:metabolism*; D013314:Stress, Mechanical; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D051416:Focal Adhesion Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
references.citation: Vascul Pharmacol. 2002 May;38(5):271-3
references.pmid: 12487031
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11295-300
references.pmid: 11572981
references.citation: PLoS One. 2009;4(3):e4853
references.pmid: 19319193
references.citation: J Biomech Eng. 1981 Aug;103(3):172-6
references.pmid: 7278195
references.citation: Mech Chem Biosyst. 2004 Dec;1(4):253-65
references.pmid: 16783922
references.citation: J Appl Physiol (1985). 2001 Aug;91(2):693-702
references.pmid: 11457783
references.citation: J Cell Physiol. 1998 Jun;175(3):323-32
references.pmid: 9572477
references.citation: Nat Rev Cancer. 2009 Feb;9(2):108-22
references.pmid: 19165226
references.citation: Am J Physiol Cell Physiol. 2008 Oct;295(4):C994-1006
references.pmid: 18701651
references.citation: J Biomech. 2006;39(14):2603-10
references.pmid: 16216252
references.citation: Biophys J. 2008 Jul;95(1):464-71
references.pmid: 18359792
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12383-8
references.pmid: 16113084
references.citation: Biol Pharm Bull. 2002 Dec;25(12):1588-92
references.pmid: 12499645
references.citation: Nature. 1995 Oct 12;377(6549):539-44
references.pmid: 7566154
references.citation: Front Biosci. 2004 Sep 01;9:3276-85
references.pmid: 15353357
references.citation: Cell Signal. 2006 Nov;18(11):1924-31
references.pmid: 16581230
references.citation: J Cell Biol. 2007 Feb 26;176(5):667-80
references.pmid: 17325207
references.citation: Am J Physiol Cell Physiol. 2009 Oct;297(4):C814-22
references.pmid: 19587216
references.citation: Exp Cell Res. 2001 Aug 1;268(1):104-14
references.pmid: 11461123
references.citation: J Biomech. 2008 Oct 20;41(14):2964-71
references.pmid: 18805531
references.citation: Nature. 2007 May 31;447(7144):592-5
references.pmid: 17538621
references.citation: Biophys J. 2008 Oct;95(7):3470-8
references.pmid: 18515393
references.citation: Cell Motil Cytoskeleton. 2008 Apr;65(4):281-94
references.pmid: 18200567
references.citation: Semin Cancer Biol. 2008 Feb;18(1):45-52
references.pmid: 17928235
references.citation: J Vasc Res. 2007;44(5):345-53
references.pmid: 17713348
references.citation: J Biomech. 2005 Sep;38(9):1895-901
references.pmid: 16023478
references.citation: Cell Motil Cytoskeleton. 2002 Aug;52(4):266-74
references.pmid: 12112140
references.citation: Biophys J. 2006 May 15;90(10):3762-73
references.pmid: 16500961
references.citation: Mol Cell Biol. 1999 Jul;19(7):4806-18
references.pmid: 10373530
references.citation: Oncogene. 1998 Jul 30;17(4):455-63
references.pmid: 9696039
references.citation: Hypertension. 2002 Feb;39(2):233-8
references.pmid: 11847190
references.citation: J Clin Invest. 1998 Jan 15;101(2):301-10
references.pmid: 9435301
references.citation: J Biol Chem. 2005 Apr 29;280(17):16546-9
references.pmid: 15760908
references.citation: Biochem Biophys Res Commun. 2001 Oct 26;288(2):356-61
references.pmid: 11606050
references.citation: J Appl Physiol (1985). 2000 Dec;89(6):2391-400
references.pmid: 11090594
references.citation: J Cell Sci. 1999 May;112 ( Pt 9):1365-73
references.pmid: 10194415
references.citation: Cardiovasc Res. 2005 Oct 1;68(1):87-97
references.pmid: 15961069