Electron microscopes can image biological macromolecules in cryogenic ice, but it shows them as low-contrast features in a grainy image (see below). Using enough electrons to reduce the graininess would first destroy the specimen.
The trick to getting enough information without frying the molecules is to image many specimens that are known to be identical, and to somehow find, align, and combine data from their images (keep in mind that these are grainy, 2D shadows of randomly oriented 3D objects). The quality of the resulting reconstruction depends heavily on the quality of the methods, and the methods are not simple.
A new report in Nature describes improved methods and a result (below) that sharpens resolution from the previous 1.3 nm to 0.66 nm. This provides about 8 times as many voxels, and gave the authors enough information to infer protein secondary structures and build a reliable atomic model of F-actin:
Raw electron cryomicroscopy images,
F-actin helical assembly.
Reconstruction at 0.66 nm resolution.
(Stereo view of density isosurface with fitted C? ribbon diagram.)
“Direct visualization of secondary structures of F-actin by electron cryomicroscopy”,
Takashi Fujii, et al., Nature 467:724–728 (2010).
The authors’ method is apparently quite practical. From the article:
We have demonstrated that our cryoEM technologies now allow us to visualize the secondary structures of such thin objects as F-actin in a few days of work, including image data collection and processing and 3D image reconstruction.
In closing, they remark that
There is also room for further improvement, to reach atomic resolution. The present work offers a new opportunity to look into cellular mechanisms essential for the activities of life.
And in building nonbiological molecular machinery, of course, it’s useful to be able to see the result.