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

Israel Patla, Tova Volberg, Nadav Elad, Vera Hirschfeld-Warneken, Carsten Grashoff, Reinhard Fässler, Joachim P. Spatz, Benjamin Geiger, Ohad Medalia

Research output: Contribution to journalArticlepeer-review

174 Scopus citations

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 languageEnglish
Pages (from-to)909-915
Number of pages7
JournalNature Cell Biology
Volume12
Issue number9
DOIs
StatePublished - 1 Sep 2010

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