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Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography

Nature Cell Biology volume 12, pages 909915 (2010) | Download Citation

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Abstract

Focal adhesions are integrin-based multiprotein complexes, several micrometres in diameter, that mechanically link the extracellular matrix with the termini of actin bundles. The molecular diversity of focal adhesions and their role in cell migration and matrix sensing has been extensively studied, but their ultrastructural architecture is still unknown. We present the first three-dimensional structural reconstruction of focal adhesions using cryo-electron tomography. Our analyses reveal that the membrane–cytoskeleton interaction at focal adhesions is mediated through particles located at the cell membrane and attached to actin fibres. The particles have diameters of 25 ± 5 nm, and an average interspacing of approximately 45 nm. Treatment with the Rho-kinase inhibitor Y-27632 induces a rapid decrease in particle diameter, suggesting that they are highly mechanosensitive. Our findings clarify the internal architecture of focal adhesions at molecular resolution, and provide insights into their scaffolding and mechanosensory functions.

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Change history

  • 17 August 2010

    In the version of this letter initially published online, Vera Hirschfeld-Warneken was incorrectly spelled in the author list. This error has been corrected in both the HTML and PDF versions of the letter.

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Acknowledgements

This study was supported by a grant from the German-Israeli Cooperation Project (DIP H.2.2) to O. M., R. F., J. S. and B. G., an NIGMS grant from the National Institutes of Health Cell Migration Consortium (Grant No. U54 GM64346) to B. G. and an ERC Starting Grant to O. M. The authors express gratitude to B. Morgenstern for help in editing the manuscript. B. G. holds the Erwin Neter Professorial Chair in Cell and Tumor Biology.

Author information

Affiliations

  1. Department of Life Sciences and the National Institute for Biotechnology in the Negev, Ben Gurion University of the Negev, Be'er-Sheva 84120, Israel.

    • Israel Patla
    • , Nadav Elad
    •  & Ohad Medalia
  2. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.

    • Tova Volberg
    •  & Benjamin Geiger
  3. Max-Planck Institute for Metals Research, Department of New Materials and Biosystems, Heisenbergstrasse, 70569 Stuttgart, Germany.

    • Vera Hirschfeld-Warneken
    •  & Joachim P. Spatz
  4. University of Heidelberg, Department of Biophysical Chemistry, Stuttgart D-70569, Germany.

    • Vera Hirschfeld-Warneken
  5. Max-Planck Institute of Biochemistry, Department of Molecular Medicine, Martinsried D-82152, Germany.

    • Carsten Grashoff
    •  & Reinhard Fässler

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Contributions

I. P., N. E., T. V., C. G. and V. H. W. performed experimental work and analysed the data. B. G., J. S., R. F. and O. M. designed the experiments, analysed the data and prepared the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Ohad Medalia.

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DOI

https://doi.org/10.1038/ncb2095

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