title: From tissue mechanics to transcription factors.
abstract: Changes in tissue stiffness are frequently associated with diseases such as cancer, fibrosis, and atherosclerosis. Several recent studies suggest that, in addition to resulting from pathology, mechanical changes may play a role akin to soluble factors in causing the progression of disease, and similar mechanical control might be essential for normal tissue development and homeostasis. Many cell types alter their structure and function in response to exogenous forces or as a function of the mechanical properties of the materials to which they adhere. This review summarizes recent progress in identifying intracellular signaling pathways, and especially transcriptional programs, that are differentially activated when cells adhere to materials with different mechanical properties or when they are subject to tension arising from external forces. Several cytoplasmic or cytoskeletal signaling pathways involving small GTPases, focal adhesion kinase and transforming growth factor beta as well as the transcriptional regulators MRTF-A, NFκB, and Yap/Taz have emerged as important mediators of mechanical signaling.
authors: Departments of Physiology and Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: janmey@mail.med.upenn.edu.
authors: Paul A
authors: PA
authors: Janmey
authors: Rebecca G
authors: RG
authors: Wells
authors: Richard K
authors: RK
authors: Assoian
authors: Christopher A
authors: CA
authors: McCulloch
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D040542:Mechanotransduction, Cellular; D013314:Stress, Mechanical; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors
keywords: Mechanical stress; Mechanosensing; Mechanotransduction; Substrate stiffness
references: Curr Opin Crit Care. 2005 Feb;11(1):82-6
references: 15659950
references: J Invest Dermatol. 2011 Dec;131(12):2378-85
references: 21776010
references: Curr Opin Neurobiol. 2009 Aug;19(4):362-9
references: 19683913
references: Cardiovasc Pathol. 2011 Nov-Dec;20(6):325-33
references: 21306921
references: Osteoarthritis Cartilage. 2011 Feb;19(2):222-32
references: 21094261
references: Mol Cell Biol. 2010 Sep;30(17):4134-48
references: 20606005
references: Physiol Rev. 2004 Oct;84(4):1097-153
references: 15383649
references: Acta Odontol Scand. 1973;31(2):109-22
references: 4516276
references: Bone. 2010 Jul;47(1):74-82
references: 20353839
references: Hepatology. 2011 Apr;53(4):1192-205
references: 21442631
references: Front Biosci. 2008 Jan 01;13:312-24
references: 17981549
references: Integr Biol (Camb). 2012 Apr;4(4):410-21
references: 22410748
references: Mol Biol Cell. 2001 Sep;12(9):2730-41
references: 11553712
references: J Dent Res. 2009 Jul;88(7):597-608
references: 19641146
references: Nat Med. 2011 Dec 11;18(1):148-52
references: 22157678
references: Sci Signal. 2012 Jun 05;5(227):ra41
references: 22669846
references: J Biol Chem. 2000 Feb 4;275(5):3088-92
references: 10652290
references: Cell Rep. 2012 Nov 29;2(5):1259-71
references: 23103162
references: J Biol Chem. 2002 Jun 21;277(25):22889-95
references: 11953441
references: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):11930-5
references: 21730131
references: Annu Rev Biomed Eng. 2012;14:431-55
references: 22655599
references: Am J Physiol Gastrointest Liver Physiol. 2013 Mar 15;304(6):G605-14
references: 23328207
references: Acta Biomater. 2013 Feb;9(2):5170-80
references: 23079022
references: J Phys Condens Matter. 2010 May 19;22(19):194120
references: 21386443
references: Microvasc Res. 2012 Jan;83(1):71-81
references: 21741394
references: Neuroreport. 2002 Dec 20;13(18):2411-5
references: 12499839
references: J Biol Chem. 2001 Aug 17;276(33):31047-52
references: 11410588
references: Biomaterials. 2009 Sep;30(27):4695-9
references: 19539367
references: J Cell Sci. 2007 May 15;120(Pt 10):1801-9
references: 17456553
references: Cell. 2001 Jun 29;105(7):851-62
references: 11439182
references: Am J Physiol Renal Physiol. 2008 May;294(5):F1116-28
references: 18337547
references: Clin Liver Dis. 2008 Nov;12(4):759-68, viii
references: 18984465
references: J Biol Chem. 2010 Mar 19;285(12):9273-81
references: 20071339
references: Trends Mol Med. 2003 Sep;9(9):376-82
references: 13129703
references: Circ Res. 2003 May 2;92(8):840-7
references: 12663487
references: J Biol Chem. 1992 Jan 15;267(2):984-9
references: 1730687
references: FEBS Lett. 2010 Oct 8;584(19):4145-50
references: 20804756
references: J Cell Sci. 1999 Sep;112 ( Pt 17):2971-81
references: 10444391
references: Invest Ophthalmol Vis Sci. 2013 Jan 14;54(1):378-86
references: 23258147
references: Eur J Cell Biol. 2006 Apr;85(3-4):175-81
references: 16546559
references: Hepatology. 2007 Aug;46(2):590-7
references: 17661407
references: Nature. 2011 Jun 08;474(7350):179-83
references: 21654799
references: Am J Physiol Gastrointest Liver Physiol. 2007 Dec;293(6):G1147-54
references: 17932231
references: Proc Natl Acad Sci U S A. 1974 Apr;71(4):1286-90
references: 4524638
references: J Periodontal Res. 2005 Apr;40(2):110-7
references: 15733145
references: Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G110-8
references: 21527725
references: Neuron. 2003 Aug 14;39(4):585-8
references: 12925273
references: Cell Biochem Biophys. 2010;56(1):1-18
references: 19842065
references: Sci Signal. 2008 Mar 11;1(10):pe13
references: 18334714
references: Dev Cell. 2004 Jun;6(6):745-6
references: 15177022
references: J Biol Chem. 2004 Mar 26;279(13):12001-4
references: 14960578
references: Curr Pharm Des. 2004;10(21):2629-41
references: 15320750
references: J Cell Sci. 2004 May 15;117(Pt 12):2449-60
references: 15159450
references: J Musculoskelet Neuronal Interact. 2007 Jan-Mar;7(1):48-53
references: 17396005
references: Biophys J. 2006 Apr 15;90(8):3012-8
references: 16461391
references: J Appl Physiol (1985). 2005 Apr;98(4):1547-53
references: 15772065
references: Am J Physiol Lung Cell Mol Physiol. 2011 Nov;301(5):L656-66
references: 21856814
references: Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):590-7
references: 21127288
references: Cancer Cell. 2011 Jun 14;19(6):776-91
references: 21665151
references: J Biomech. 2012 Mar 15;45(5):824-31
references: 22196970
references: Am J Physiol. 1997 May;272(5 Pt 1):C1654-63
references: 9176157
references: Cell. 2003 May 2;113(3):329-42
references: 12732141
references: J Cell Biol. 2010 Aug 23;190(4):693-706
references: 20733059
references: Am J Respir Crit Care Med. 2012 Nov 1;186(9):866-76
references: 22936357
references: Cell. 2005 Dec 2;123(5):903-15
references: 16325583
references: J Cell Biol. 2007 Dec 17;179(6):1311-23
references: 18086923
references: Nature. 1999 Apr 1;398(6726):422-6
references: 10201372
references: J Biomed Sci. 2009 Jan 22;16:12
references: 19272177
references: Cardiovasc Res. 2000 May;46(2):257-63
references: 10773229
references: Nat Cell Biol. 2010 Jul;12(7):711-8
references: 20581838
references: Nat Clin Pract Cardiovasc Med. 2009 Jan;6(1):16-26
references: 19029993
references: Nat Rev Mol Cell Biol. 2012 Sep;13(9):591-600
references: 22895435
references: Nat Cell Biol. 2010 Jun;12(6):533-42
references: 20453849
references: Curr Biol. 2012 Nov 6;22(21):2017-26
references: 23063436
references: Biochim Biophys Acta. 2009 May;1793(5):911-20
references: 19339214
references: Nat Commun. 2012 Feb 14;3:671
references: 22334074
references: Front Biosci (Landmark Ed). 2009 Jan 01;14(1):45-58
references: 19273053
references: Nature. 2009 Feb 26;457(7233):1103-8
references: 19242469
references: Curr Drug Targets CNS Neurol Disord. 2004 Aug;3(4):287-95
references: 15379605
references: Mol Cell Biol. 2009 Sep;29(18):5104-14
references: 19596792
references: Annu Rev Biomed Eng. 2004;6:275-302
references: 15255771
references: J Biol Chem. 1997 Apr 18;272(16):10948-56
references: 9099754
references: Circ Res. 2010 Nov 12;107(10):1265-74
references: 20884880
references: Am J Respir Cell Mol Biol. 2012 Sep;47(3):340-8
references: 22461426
references: Cell Motil Cytoskeleton. 2005 Jan;60(1):24-34
references: 15573414
references: Curr Biol. 2009 Sep 29;19(18):1511-8
references: 19765988
references: Mol Cancer. 2010 Feb 10;9:35
references: 20144241
references: PLoS One. 2009;4(4):e5262
references: 19370157
references: Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13420-5
references: 21813757
references: Biophys J. 2009 Oct 7;97(7):1883-90
references: 19804718
references: Cell. 2005 Dec 2;123(5):889-901
references: 16325582
references: Curr Atheroscler Rep. 2007 Aug;9(2):139-44
references: 17877923
references: Am J Physiol Cell Physiol. 2008 Apr;294(4):C1056-66
references: 18272820
references: Am J Pathol. 2005 May;166(5):1343-51
references: 15855636
references: J Biol Chem. 2002 Dec 6;277(49):47541-50
references: 12324467
references: Exp Eye Res. 2013 Aug;113:66-73
references: 23727052
references: Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14855-60
references: 12397177
references: Nat Rev Mol Cell Biol. 2002 May;3(5):349-63
references: 11988769
references: J Cell Sci. 2007 Nov 1;120(Pt 21):3895-904
references: 17940065
references: Nat Rev Mol Cell Biol. 2004 Aug;5(8):614-25
references: 15366705
references: J Cell Sci. 2003 Apr 15;116(Pt 8):1397-408
references: 12640025
references: Microsc Microanal. 2005 Jun;11(3):200-8
references: 16060972
references: Curr Opin Crit Care. 2008 Feb;14(1):87-93
references: 18195632
references: Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13661-5
references: 9391082
references: J Biol Chem. 2006 Oct 20;281(42):31720-8
references: 16908522
references: Cell Biochem Funct. 2003 Sep;21(3):223-9
references: 12910474
references: Biophys J. 2008 Jun;94(12):4984-95
references: 18326659
references: Biophys J. 2009 Jun 17;96(12):5095-102
references: 19527669
references: Cell Tissue Res. 1981;220(2):325-35
references: 7197588
references: Biomaterials. 2009 Dec;30(36):6867-78
references: 19775749
references: J Biol Chem. 2001 Sep 21;276(38):35967-77
references: 11466312
references: Biotechnol Bioeng. 2013 Aug;110(8):2301-10
references: 23436578
references: Mol Cell Biol. 2005 Apr;25(8):3173-81
references: 15798203
references: J Biol Chem. 2011 Mar 4;286(9):7018-26
references: 21224387
references: Hepatology. 2007 Oct;46(4):1246-56
references: 17625791
references: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18499-504
references: 20937855
references: Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1252-66
references: 21257918
references: Biol Cell. 2006 Dec;98(12):721-30
references: 16895521
references: Circulation. 2010 Feb 2;121(4):505-11
references: 20083680
references: Circ Res. 2008 Aug 29;103(5):477-84
references: 18669921