Low-Dose Electron Microscopy of Individual Biological Macromolecules

Structural details at a resolution in the range 7–15 Å have now been demonstrated for a number of biological macromolecules [1, 2, 13]. The main limitation to visualizing such high-resolution details has been the damage to macromolecular fine structure caused by the large electron dosages employed in conventional electron microscopy [8]. Reduction of electron dosages, however, results in recorded images with an extremely poor signal- to-noise ratio. This ratio is further reduced by the need to sacrifice conventional staining methods if one aims at high resolution. This problem has been effectively overcome by averaging over a large number of unit cells, which is easy to achieve for the ordered two- dimensional arrays which occur in a number of biological objects.