|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online January 27, 2006
doi: 10.1242/10.1242/jcs.02760
Research Article |

1 Vascular Biology Program, Departments of Pathology and Surgery, Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
2 Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02115, USA
Author for correspondence (e-mail: donald.ingber{at}childrens.harvard.edu)
Accepted 24 October 2005
To understand how cells sense and adapt to mechanical stress, we applied tensional forces to magnetic microbeads bound to cell-surface integrin receptors and measured changes in bead displacement with sub-micrometer resolution using optical microscopy. Cells exhibited four types of mechanical responses: (1) an immediate viscoelastic response; (2) early adaptive behavior characterized by pulse-to-pulse attenuation in response to oscillatory forces; (3) later adaptive cell stiffening with sustained (>15 second) static stresses; and (4) a large-scale repositioning response with prolonged (>1 minute) stress. Importantly, these adaptation responses differed biochemically. The immediate and early responses were affected by chemically dissipating cytoskeletal prestress (isometric tension), whereas the later adaptive response was not. The repositioning response was prevented by inhibiting tension through interference with Rho signaling, similar to the case of the immediate and early responses, but it was also prevented by blocking mechanosensitive ion channels or by inhibiting Src tyrosine kinases. All adaptive responses were suppressed by cooling cells to 4°C to slow biochemical remodeling. Thus, cells use multiple mechanisms to sense and respond to static and dynamic changes in the level of mechanical stress applied to integrins.
Key words: Integrin, Focal adhesion, Mechanotransduction, Prestress, Tension, Magnetometry
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
![]() |
J. D. Paulus, G. B. Willer, J. R. Willer, R. G. Gregg, and M. C. Halloran Muscle Contractions Guide Rohon-Beard Peripheral Sensory Axons J. Neurosci., October 21, 2009; 29(42): 13190 - 13201. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Roca-Cusachs, N. C. Gauthier, A. del Rio, and M. P. Sheetz Clustering of {alpha}5{beta}1 integrins determines adhesion strength whereas {alpha}v{beta}3 and talin enable mechanotransduction PNAS, September 22, 2009; 106(38): 16245 - 16250. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. K. Thodeti, B. Matthews, A. Ravi, A. Mammoto, K. Ghosh, A. L. Bracha, and D. E. Ingber TRPV4 Channels Mediate Cyclic Strain-Induced Endothelial Cell Reorientation Through Integrin-to-Integrin Signaling Circ. Res., May 8, 2009; 104(9): 1123 - 1130. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Huveneers and E. H. J. Danen Adhesion signaling - crosstalk between integrins, Src and Rho J. Cell Sci., April 15, 2009; 122(8): 1059 - 1069. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Nagayama and T. Matsumoto Contribution of actin filaments and microtubules to quasi-in situ tensile properties and internal force balance of cultured smooth muscle cells on a substrate Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1569 - C1578. [Abstract] [Full Text] [PDF] |
||||
![]() |
W. Zheng, L. P. Christensen, and R. J. Tomanek Differential effects of cyclic and static stretch on coronary microvascular endothelial cell receptors and vasculogenic/angiogenic responses Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H794 - H800. [Abstract] [Full Text] [PDF] |
||||
![]() |
I. D Campbell The Croonian lecture 2006 Structure of the living cell Phil Trans R Soc B, July 27, 2008; 363(1502): 2379 - 2391. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Quinlan, N. G. Docherty, R. W. G. Watson, and J. M. Fitzpatrick Exploring mechanisms involved in renal tubular sensing of mechanical stretch following ureteric obstruction Am J Physiol Renal Physiol, July 1, 2008; 295(1): F1 - F11. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Na, O. Collin, F. Chowdhury, B. Tay, M. Ouyang, Y. Wang, and N. Wang Rapid signal transduction in living cells is a unique feature of mechanotransduction PNAS, May 6, 2008; 105(18): 6626 - 6631. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. F. Ramos and W. D. Stamer Effects of Cyclic Intraocular Pressure on Conventional Outflow Facility Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 275 - 281. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. T. B. Nguyen and J. J. Fredberg Strange Dynamics of a Dynamic Cytoskeleton Proceedings of the ATS, January 1, 2008; 5(1): 58 - 61. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. J. Sniadecki, A. Anguelouch, M. T. Yang, C. M. Lamb, Z. Liu, S. B. Kirschner, Y. Liu, D. H. Reich, and C. S. Chen From the Cover: Magnetic microposts as an approach to apply forces to living cells PNAS, September 11, 2007; 104(37): 14553 - 14558. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. P. Desai, S. E. Sinclair, K. E. Chapman, A. Hassid, and C. M. Waters High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L769 - L778. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Chien Mechanotransduction and endothelial cell homeostasis: the wisdom of the cell Am J Physiol Heart Circ Physiol, March 1, 2007; 292(3): H1209 - H1224. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Mammoto, S. Huang, and D. E. Ingber Filamin links cell shape and cytoskeletal structure to Rho regulation by controlling accumulation of p190RhoGAP in lipid rafts J. Cell Sci., February 1, 2007; 120(3): 456 - 467. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. E. Ingber Cellular mechanotransduction: putting all the pieces together again FASEB J, May 1, 2006; 20(7): 811 - 827. [Abstract] [Full Text] [PDF] |
||||