| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
VASCULAR BIOLOGY
1Department of Mechanical Engineering and Biological Engineering Division, Massachusetts Institute of Technology, Cambridge 02139; and 2Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
Submitted 12 December 2003 ; accepted in final form 3 June 2004
Vascular endothelial cells rapidly transduce local mechanical forces into biological signals through numerous processes including the activation of focal adhesion sites. To examine the mechanosensing capabilities of these adhesion sites, focal adhesion translocation was monitored over the course of 5 min with GFP-paxillin while applying nN-level magnetic trap shear forces to the cell apex via integrin-linked magnetic beads. A nongraded steady-load threshold for mechanotransduction was established between 0.90 and 1.45 nN. Activation was greatest near the point of forcing (<7.5 µm), indicating that shear forces imposed on the apical cell membrane transmit nonuniformly to the basal cell surface and that focal adhesion sites may function as individual mechanosensors responding to local levels of force. Results from a continuum, viscoelastic finite element model of magnetocytometry that represented experimental focal adhesion attachments provided support for a nonuniform force transmission to basal surface focal adhesion sites. To further understand the role of force transmission on focal adhesion activation and dynamics, sinusoidally varying forces were applied at 0.1, 1.0, 10, and 50 Hz with a 1.45 nN offset and a 2.25 nN maximum. At 10 and 50 Hz, focal adhesion activation did not vary with spatial location, as observed for steady loading, whereas the response was minimized at 1.0 Hz. Furthermore, applying the tyrosine kinase inhibitors genistein and PP2, a specific Src family kinase inhibitor, showed tyrosine kinase signaling has a role in force-induced translocation. These results highlight the mutual importance of force transmission and biochemical signaling in focal adhesion mechanotransduction.
mechanotransduction; endothelial cell; paxillin; viscoelastic model
This article has been cited by other articles:
|
|
 |
|
  N. Gavara, P. Roca-Cusachs, R. Sunyer, R. Farre, and D. Navajas Mapping Cell-Matrix Stresses during Stretch Reveals Inelastic Reorganization of the Cytoskeleton Biophys. J., July 1, 2008; 95(1): 464 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Matthews, D. R. Overby, R. Mannix, and D. E. Ingber Cellular adaptation to mechanical stress: role of integrins, Rho, cytoskeletal tension and mechanosensitive ion channels J. Cell Sci., February 1, 2006; 119(3): 508 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yoshigi, L. M. Hoffman, C. C. Jensen, H. J. Yost, and M. C. Beckerle Mechanical force mobilizes zyxin from focal adhesions to actin filaments and regulates cytoskeletal reinforcement J. Cell Biol., October 24, 2005; 171(2): 209 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Deng, N. J. Fairbank, D. J. Cole, J. J. Fredberg, and G. N. Maksym Airway smooth muscle tone modulates mechanically induced cytoskeletal stiffening and remodeling J Appl Physiol, August 1, 2005; 99(2): 634 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Bellott, K. C. Patel, and T. J. Burkholder Reduction of caveolin-3 expression does not inhibit stretch-induced phosphorylation of ERK2 in skeletal muscle myotubes J Appl Physiol, April 1, 2005; 98(4): 1554 - 1561. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
