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Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics

Publication ,  Journal Article
Grashoff, C; Hoffman, BD; Brenner, MD; Zhou, R; Parsons, M; Yang, MT; McLean, MA; Sligar, SG; Chen, CS; Ha, T; Schwartz, MA
Published in: Nature
2010

Mechanical forces are central to developmental, physiological and pathological processes1. However, limited understanding of force transmission within sub-cellular structures is a major obstacle to unravelling molecular mechanisms. Here we describe the development of a calibrated biosensor that measures forces across specific proteins in cells with piconewton (pN) sensitivity, as demonstrated by single molecule fluorescence force spectroscopy2. The method is applied to vinculin, a protein that connects integrins to actin filaments and whose recruitment to focal adhesions (FAs) is forcedependent3. We show that tension across vinculin in stable FAs is ∼2.5pN and that vinculin recruitment to FAs and force transmission across vinculin are regulated separately. Highest tension across vinculin is associated with adhesion assembly and enlargement. Conversely, vinculin is under low force in disassembling or sliding FAs at the trailing edge of migrating cells. Furthermore, vinculin is required for stabilizing adhesions under force. Together, these data reveal that FA stabilization under force requires both vinculin recruitment and force transmission, and that, surprisingly, these processes can be controlled independently. © 2010 Macmillan Publishers Limited. All rights reserved.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

2010

Volume

466

Issue

7303

Start / End Page

263 / 266

Related Subject Headings

  • Vinculin
  • Stress, Mechanical
  • Spectrometry, Fluorescence
  • Optical Tweezers
  • Movement
  • Microscopy, Confocal
  • Mice
  • Humans
  • General Science & Technology
  • Focal Adhesions
 

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Grashoff, C., Hoffman, B. D., Brenner, M. D., Zhou, R., Parsons, M., Yang, M. T., … Schwartz, M. A. (2010). Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature, 466(7303), 263–266. https://doi.org/10.1038/nature09198
Grashoff, C., B. D. Hoffman, M. D. Brenner, R. Zhou, M. Parsons, M. T. Yang, M. A. McLean, et al. “Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics.” Nature 466, no. 7303 (2010): 263–66. https://doi.org/10.1038/nature09198.
Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature. 2010;466(7303):263–6.
Grashoff, C., et al. “Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics.” Nature, vol. 466, no. 7303, 2010, pp. 263–66. Scival, doi:10.1038/nature09198.
Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, McLean MA, Sligar SG, Chen CS, Ha T, Schwartz MA. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature. 2010;466(7303):263–266.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

2010

Volume

466

Issue

7303

Start / End Page

263 / 266

Related Subject Headings

  • Vinculin
  • Stress, Mechanical
  • Spectrometry, Fluorescence
  • Optical Tweezers
  • Movement
  • Microscopy, Confocal
  • Mice
  • Humans
  • General Science & Technology
  • Focal Adhesions