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

Abstract

Little is known about the ultrastructure of focal adhesions, compared with their extensive molecular characterization. Cryo-electron tomography provides novel insights into the internal sub-structures at the interface between adhesions and the actin cytoskeleton. 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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Patla, I., Volberg, T., Elad, N. et al. Dissecting the molecular architecture of integrin adhesion sites by cryo-electron tomography. Nat Cell Biol 12, 909–915 (2010). https://doi.org/10.1038/ncb2095

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