Method for the Observation of Macromolecules with the Electron Microscope Illustrated with Micrographs of DNA

The theoretical limit of resolving power for transmission electron microscopes is in the range 5 to 10 A and it is not unusual for resolutions in the range 10 to 20 A to be reported in practice. This means that the dimensions of a large dass of biologically important molecules and synthetic polymers should be directly observable if contrast and other limitations could be overcome. For example, a spherical protein molecule with a diameter of 20 A would have a molecular weight of only about 3500. Except for a few isolated instances, however, electron microscopy as a means for determining molecular size and shape has largely been confined to the study of very large macromolecules which have molecular weights of several millions and dimensions of several hundred angstroms. The reasons for the relative ineffectiveness of the electron microscope for the study of the smaller organic particles are their low electron-scattering power, the difficulty of distinguishing them from their surroundings or substrate, and in many instances the destruction or distortion of structure resulting from the removal of water.