| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Department of Physiology, University of Massachusetts Medical School, Worcester 01605; and 2 Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215
One of the hallmarks of oncogenic transformation is anchorage-independent growth (27). Here we demonstrate that responses to substrate rigidity play a major role in distinguishing the growth behavior of normal cells from that of transformed cells. We cultured normal or H-ras-transformed NIH 3T3 cells on flexible collagen-coated polyacrylamide substrates with similar chemical properties but different rigidity. Compared with cells cultured on stiff substrates, nontransformed cells on flexible substrates showed a decrease in the rate of DNA synthesis and an increase in the rate of apoptosis. These responses on flexible substrates are coupled to decreases in cell spreading area and traction forces. In contrast, transformed cells maintained their growth and apoptotic characteristics regardless of substrate flexibility. The responses in cell spreading area and traction forces to substrate flexibility were similarly diminished. Our results suggest that normal cells are capable of probing substrate rigidity and that proper mechanical feedback is required for regulating cell shape, cell growth, and survival. The loss of this response can explain the unregulated growth of transformed cells.
mechanical signaling; cell cycle; cell shape; traction force; cancer
This article has been cited by other articles:
|
|
 |
|
  D. Icard-Arcizet, O. Cardoso, A. Richert, and S. Henon Cell Stiffening in Response to External Stress is Correlated to Actin Recruitment Biophys. J., April 1, 2008; 94(7): 2906 - 2913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Schlunck, H. Han, T. Wecker, D. Kampik, T. Meyer-ter-Vehn, and F. Grehn Substrate Rigidity Modulates Cell Matrix Interactions and Protein Expression in Human Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 262 - 269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Solon, I. Levental, K. Sengupta, P. C. Georges, and P. A. Janmey Fibroblast Adaptation and Stiffness Matching to Soft Elastic Substrates Biophys. J., December 15, 2007; 93(12): 4453 - 4461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kostic, J. Sap, and M. P. Sheetz RPTP{alpha} is required for rigidity-dependent inhibition of extension and differentiation of hippocampal neurons J. Cell Sci., November 1, 2007; 120(21): 3895 - 3904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. A. Harley, T. M. Freyman, M. Q. Wong, and L. J. Gibson A New Technique for Calculating Individual Dermal Fibroblast Contractile Forces Generated within Collagen-GAG Scaffolds Biophys. J., October 15, 2007; 93(8): 2911 - 2922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-h. Guo, M. T. Frey, N. A. Burnham, and Y.-l. Wang Substrate Rigidity Regulates the Formation and Maintenance of Tissues Biophys. J., March 15, 2006; 90(6): 2213 - 2220. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Jiang, A. H. Huang, Y. Cai, M. Tanase, and M. P. Sheetz Rigidity Sensing at the Leading Edge through {alpha}v{beta}3 Integrins and RPTP{alpha} Biophys. J., March 1, 2006; 90(5): 1804 - 1809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Fassett, D. Tobolt, and L. K. Hansen Type I Collagen Structure Regulates Cell Morphology and EGF Signaling in Primary Rat Hepatocytes through cAMP-dependent Protein Kinase A Mol. Biol. Cell, January 1, 2006; 17(1): 345 - 356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Discher, P. Janmey, and Y.-l. Wang Tissue Cells Feel and Respond to the Stiffness of Their Substrate Science, November 18, 2005; 310(5751): 1139 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Reinhart-King, M. Dembo, and D. A. Hammer The Dynamics and Mechanics of Endothelial Cell Spreading Biophys. J., July 1, 2005; 89(1): 676 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Georges and P. A. Janmey Cell type-specific response to growth on soft materials J Appl Physiol, April 1, 2005; 98(4): 1547 - 1553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Griffin, S. Sen, H. L. Sweeney, and D. E. Discher Adhesion-contractile balance in myocyte differentiation J. Cell Sci., November 15, 2004; 117(24): 5855 - 5863. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Engler, M. A. Griffin, S. Sen, C. G. Bonnemann, H. L. Sweeney, and D. E. Discher Myotubes differentiate optimally on substrates with tissue-like stiffness: pathological implications for soft or stiff microenvironments J. Cell Biol., September 13, 2004; 166(6): 877 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Mechanisms and Limits of Induced Postnatal Lung Growth Am. J. Respir. Crit. Care Med., August 1, 2004; 170(3): 319 - 343. [Full Text] [PDF]
|
|
|
|
|
|
S. Vanni, B. C. Lagerholm, C. Otey, D. L. Taylor, and F. Lanni Internet-Based Image Analysis Quantifies Contractile Behavior of Individual Fibroblasts inside Model Tissue Biophys. J., April 1, 2003; 84(4): 2715 - 2727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y. Koo, D. J. Irvine, A. M. Mayes, D. A. Lauffenburger, and L. G. Griffith Co-regulation of cell adhesion by nanoscale RGD organization and mechanical stimulus J. Cell Sci., January 4, 2002; 115(7): 1423 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-B. Wang, M. Dembo, S. K. Hanks, and Y.-l. Wang Focal adhesion kinase is involved in mechanosensing during fibroblast migration PNAS, September 25, 2001; 98(20): 11295 - 11300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Stamenovic, S. M. Mijailovich, I. M. Tolic-Norrelykke, J. Chen, and N. Wang Cell prestress. II. Contribution of microtubules Am J Physiol Cell Physiol, March 1, 2002; 282(3): C617 - C624. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
