Discrimination of protein and nucleic acids by electron microscopy using contrast variation

A contrast variation method is described by which protein and nucleic acid components of nucleoprotein assemblies can be distinguished in the electron microscope. Using contrasting media of variable electron scattering density, the contribution to image contrast of protein or nucleic acid can be matched out. The protein and DNA components of T4 bacteriophages were visualized separately in this way. The distribution of RNA and protein in ribosomes was studied by processing images of crystalline sheets of ribosomes embedded in a range of contrasting media. Projection maps of crystalline ribosomes suggest that the ribosomal RNA is located predominantly in the central region of the particle.