A new approach for the visualization of molecular arrangement in biological micro-crystals

Biological molecules often form micro-crystals that are in a size range that is unsuited for study either by X-ray crystallography or by electron microscopy. The method described here allows the use of most of these crystals. It consists of cutting sections through the crystal deposited on a grid after a preliminary observation in the electron microscope to determine its precise location. It allows visualization of the crystal molecular packing in any plane normal to the grid plane at the resolution usually obtained by negative staining. If the crystal is thin enough, two orthogonal views of the same crystal can be obtained. The orientation and the position of the sections along the crystal axis are precisely determined using latex particles as reference points. Crystals as small as 1 micrometer in length can be studied.