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 45Å 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.
| Original language | English |
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| Pages (from-to) | 909-915 |
| Number of pages | 7 |
| Journal | Nature Cell Biology |
| Volume | 12 |
| Issue number | 9 |
| DOIs | |
| Publication status | Published - Sept 2010 |
Funding
German-Israeli Cooperation Project [DIP H.2.2]; National Institutes of Health Cell Migration Consortium [U54 GM64346]; ERCThis 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.
All Science Journal Classification (ASJC) codes
- Cell Biology