Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Tissue Cells Feel and Respond to the Stiffness of Their Substrate
Dennis E. Discher,1*Paul Janmey,1Yu-li Wang2
Normal tissue cells are generally not viable when suspendedin a fluid and are therefore said to be anchorage dependent.Such cells must adhere to a solid, but a solid can be as rigidas glass or softer than a baby's skin. The behavior of somecells on soft materials is characteristic of important phenotypes;for example, cell growth on soft agar gels is used to identifycancer cells. However, an understanding of how tissue cellsincludingfibroblasts, myocytes, neurons, and other cell typessensematrix stiffness is just emerging with quantitative studiesof cells adhering to gels (or to other cells) with which elasticitycan be tuned to approximate that of tissues. Key roles in molecularpathways are played by adhesion complexes and the actinmyosincytoskeleton, whose contractile forces are transmitted throughtranscellular structures. The feedback of local matrix stiffnesson cell state likely has important implications for development,differentiation, disease, and regeneration.
1 School of Engineering and Applied Science and Cell and Molecular Biology Graduate Group, University of Pennsylvania, Philadelphia, PA 191046315, USA. 2 Departments of Physiology and Cell Biology, University of Massachusetts, Worcester, MA 01655, USA.
* To whom correspondence should be addressed. E-mail: discher{at}seas.upenn.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
INTRODUCTION TO SPECIAL ISSUE
Marc Lavine, Valda Vinson, and Robert Coontz (18 November 2005) Science310 (5751), 1131.
[DOI: 10.1126/science.310.5751.1131] |Summary »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mechanical Forces Induced by the Transendothelial Migration of Human Neutrophils.
A. Rabodzey, P. Alcaide, F. W. Luscinskas, and B. Ladoux (2008)
Biophys. J.
95, 1428-1438
|Abstract »|Full Text »|PDF »
Measurement Techniques for Cellular Biomechanics In Vitro.
K. A. Addae-Mensah and J. P. Wikswo (2008)
Experimental Biology and Medicine
233, 792-809
|Abstract »|Full Text »|PDF »
Nuclear Shape, Mechanics, and Mechanotransduction.
K. N. Dahl, A. J.S. Ribeiro, and J. Lammerding (2008)
Circ. Res.
102, 1307-1318
|Abstract »|Full Text »|PDF »
Directional control of cell motility through focal adhesion positioning and spatial control of Rac activation.
N. Xia, C. K. Thodeti, T. P. Hunt, Q. Xu, M. Ho, G. M. Whitesides, R. Westervelt, and D. E. Ingber (2008)
FASEB J
22, 1649-1659
|Abstract »|Full Text »|PDF »
X. Zhou, R. G. Rowe, N. Hiraoka, J. P. George, D. Wirtz, D. F. Mosher, I. Virtanen, M. A. Chernousov, and S. J. Weiss (2008)
Genes & Dev.
22, 1231-1243
|Abstract »|Full Text »|PDF »
Collagen Fibril Flow and Tissue Translocation Coupled to Fibroblast Migration in 3D Collagen Matrices.
M. Miron-Mendoza, J. Seemann, and F. Grinnell (2008)
Mol. Biol. Cell
19, 2051-2058
|Abstract »|Full Text »|PDF »
Soft Substrate Up-regulates the Interaction of STIM1 with Store-operated Ca2+ Channels That Lead to Normal Epithelial Cell Apoptosis.
W.-T. Chiu, M.-J. Tang, H.-C. Jao, and M.-R. Shen (2008)
Mol. Biol. Cell
19, 2220-2230
|Abstract »|Full Text »|PDF »
Matrix Elasticity, Cytoskeletal Tension, and TGF-{beta}: The Insoluble and Soluble Meet.
The transglutaminase 2 gene (TGM2), a potential molecular marker for chemotherapeutic drug sensitivity, is epigenetically silenced in breast cancer.
L. Ai, W.-J. Kim, B. Demircan, L. M. Dyer, K. J. Bray, R. R. Skehan, N. A. Massoll, and K. D. Brown (2008)
Carcinogenesis
29, 510-518
|Abstract »|Full Text »|PDF »
Do Cells Sense Stress or Strain? Measurement of Cellular Orientation Can Provide a Clue.
Propagation of Mechanical Stress through the Actin Cytoskeleton toward Focal Adhesions: Model and Experiment.
R. Paul, P. Heil, J. P. Spatz, and U. S. Schwarz (2008)
Biophys. J.
94, 1470-1482
|Abstract »|Full Text »|PDF »
Cell adaptive response to extracellular matrix density is controlled by ICAP-1-dependent {beta}1-integrin affinity.
A. Millon-Fremillon, D. Bouvard, A. Grichine, S. Manet-Dupe, M. R. Block, and C. Albiges-Rizo (2008)
J. Cell Biol.
180, 427-441
|Abstract »|Full Text »|PDF »
Paxillin-dependent stimulation of microtubule catastrophes at focal adhesion sites.
A. Efimov, N. Schiefermeier, I. Grigoriev, M. C. Brown, C. E. Turner, J. V. Small, and I. Kaverina (2008)
J. Cell Sci.
121, 196-204
|Abstract »|Full Text »|PDF »
Substrate Rigidity Modulates Cell Matrix Interactions and Protein Expression in Human Trabecular Meshwork Cells.
G. Schlunck, H. Han, T. Wecker, D. Kampik, T. Meyer-ter-Vehn, and F. Grehn (2008)
Invest. Ophthalmol. Vis. Sci.
49, 262-269
|Abstract »|Full Text »|PDF »
High Resolution Traction Force Microscopy Based on Experimental and Computational Advances.
B. Sabass, M. L. Gardel, C. M. Waterman, and U. S. Schwarz (2008)
Biophys. J.
94, 207-220
|Abstract »|Full Text »|PDF »
Fibroblast Adaptation and Stiffness Matching to Soft Elastic Substrates.
J. Solon, I. Levental, K. Sengupta, P. C. Georges, and P. A. Janmey (2007)
Biophys. J.
93, 4453-4461
|Abstract »|Full Text »|PDF »
Structural basis of filamin A functions.
F. Nakamura, T. M. Osborn, C. A. Hartemink, J. H. Hartwig, and T. P. Stossel (2007)
J. Cell Biol.
179, 1011-1025
|Abstract »|Full Text »|PDF »
Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis.
P. C. Georges, J.-J. Hui, Z. Gombos, M. E. McCormick, A. Y. Wang, M. Uemura, R. Mick, P. A. Janmey, E. E. Furth, and R. G. Wells (2007)
Am J Physiol Gastrointest Liver Physiol
293, G1147-G1154
|Abstract »|Full Text »|PDF »
Phase Transitions of the Coupled Membrane-Cytoskeleton Modify Cellular Shape.
Z. Ma, D. P. Myers, R. F. Wu, F. E. Nwariaku, and L. S. Terada (2007)
J. Cell Biol.
179, 23-31
|Abstract »|Full Text »|PDF »
A High-Throughput Soft Agar Assay for Identification of Anticancer Compound.
S. N. Anderson, D. L. Towne, D. J. Burns, and U. Warrior (2007)
J Biomol Screen
12, 938-945
|Abstract »|PDF »
Smooth muscle cell rigidity and extracellular matrix organization influence endothelial cell spreading and adhesion formation in coculture.
C. S. Wallace, S. A. Strike, and G. A. Truskey (2007)
Am J Physiol Heart Circ Physiol
293, H1978-H1986
|Abstract »|Full Text »|PDF »
Alterations in Lateral Left Ventricular Wall Transmural Strains During Acute Circumflex and Anterior Descending Coronary Occlusion.
F. Langer, F. Rodriguez, A. Cheng, S. Ortiz, K. B. Harrington, M. K. Zasio, G. T. Daughters, J. C. Criscione, N. B. Ingels, and D. C. Miller (2007)
Ann. Thorac. Surg.
84, 51-60
|Abstract »|Full Text »|PDF »
A new microrheometric approach reveals individual and cooperative roles for TGF-{beta}1 and IL-1{beta} in fibroblast-mediated stiffening of collagen gels.
L. Y. Leung, D. Tian, C. P. Brangwynne, D. A. Weitz, and D. J. Tschumperlin (2007)
FASEB J
21, 2064-2073
|Abstract »|Full Text »|PDF »
Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates.
A. Saez, M. Ghibaudo, A. Buguin, P. Silberzan, and B. Ladoux (2007)
PNAS
104, 8281-8286
|Abstract »|Full Text »|PDF »
Overexpression of Carcinoma and Embryonic Cytotrophoblast Cell-Specific Mig-7 Induces Invasion and Vessel-Like Structure Formation.
A. P. Petty, K. L. Garman, V. D. Winn, C. M. Spidel, and J. S. Lindsey (2007)
Am. J. Pathol.
170, 1763-1780
|Abstract »|Full Text »|PDF »
Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy.
C. B. Raub, V. Suresh, T. Krasieva, J. Lyubovitsky, J. D. Mih, A. J. Putnam, B. J. Tromberg, and S. C. George (2007)
Biophys. J.
92, 2212-2222
|Abstract »|Full Text »|PDF »
Septal-lateral annnular cinching perturbs basal left ventricular transmural strains.
T. C. Nguyen, A. Cheng, F. A. Tibayan, D. Liang, G. T. Daughters, N. B. Ingels Jr., and D. C. Miller (2007)
Eur. J. Cardiothorac. Surg.
31, 423-429
|Abstract »|Full Text »|PDF »
Forced Unfolding of Coiled-Coils in Fibrinogen by Single-Molecule AFM.
A. E. X. Brown, R. I. Litvinov, D. E. Discher, and J. W. Weisel (2007)
Biophys. J.
92, L39-L41
|Abstract »|Full Text »|PDF »
Antiadhesive effect of fibrinogen: a safeguard for thrombus stability.
Differences in Chlamydia trachomatis Serovar E Growth Rate in Polarized Endometrial and Endocervical Epithelial Cells Grown in Three-Dimensional Culture.
N. V. Guseva, S. Dessus-Babus, C. G. Moore, J. D. Whittimore, and P. B. Wyrick (2007)
Infect. Immun.
75, 553-564
|Abstract »|Full Text »|PDF »
Nonequilibrium Mechanics of Active Cytoskeletal Networks.
D. Mizuno, C. Tardin, C. F. Schmidt, and F. C. MacKintosh (2007)
Science
315, 370-373
|Abstract »|Full Text »|PDF »
Altered Myocardial Shear Strains Are Associated With Chronic Ischemic Mitral Regurgitation.
T. C. Nguyen, A. Cheng, F. Langer, F. Rodriguez, R. A. Oakes, A. Itoh, D. B. Ennis, D. Liang, G. T. Daughters, N. B. Ingels Jr, et al. (2007)
Ann. Thorac. Surg.
83, 47-54
|Abstract »|Full Text »|PDF »
Identification of a Stage-Specific Permissive In Vitro Culture Environment for Follicle Growth and Oocyte Development.
M. Xu, E. West, L. D. Shea, and T. K. Woodruff (2006)
Biol Reprod
75, 916-923
|Abstract »|Full Text »|PDF »
Viscoelastic properties of individual glial cells and neurons in the CNS.
Y.-B. Lu, K. Franze, G. Seifert, C. Steinhauser, F. Kirchhoff, H. Wolburg, J. Guck, P. Janmey, E.-Q. Wei, J. Kas, et al. (2006)
PNAS
103, 17759-17764
|Abstract »|Full Text »|PDF »
Matrices with Compliance Comparable to that of Brain Tissue Select Neuronal over Glial Growth in Mixed Cortical Cultures.
P. C. Georges, W. J. Miller, D. F. Meaney, E. S. Sawyer, and P. A. Janmey (2006)
Biophys. J.
90, 3012-3018
|Abstract »|Full Text »|PDF »
Exploring and Engineering the Cell Surface Interface.