Defining the precise organization of cellular actin filaments is an important goal of cytoskeletal research and will allow us to understand how protrusive force is generated in motile cells. The current model of a`treadmilling' branched actin array is compelling but based on electron microscopy, and so there is always the worry that the picture is distorted by preparation artefacts. One approach that avoids preparative steps that generate such artefacts is cryo-EM, but its application has been limited to objects in aqueous suspensions. Gunter Resch and co-workers now reveal that cryo-EM can be applied to cytoskeletons (see). They have grown cells on holey carbon support films and embedded the extracted cytoskeletons in a layer of vitreous ice. Combining video microscopy and cryo-EM, they have been able to view the organization of the cytoskeleton in lamellipodia/filopodia with unprecedented clarity. Ultimately, this method will allow investigators to discriminate between different models of lamellipodial protrusion, revealing, for example, the extent of actin branching and the precise location of lamellipodial proteins.
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