Macromolecular crystal structure and properties as revealed by atomic force microscopy

Atomic force microscopy (AFM) has been used to study protein, nucleic acid, and virus crystals in situ, in their mother liquors, as they grow. From sequential AFM images taken at brief intervals over many hours, or even days, the mechanisms and kinetics of the growth process can be defined. The appearance of both two and three-dimensional nuclei on crystal surfaces have been visualized, defect structures were clearly evident and defect densities of crystals were also determined. The incorporation of a wide range of impurities ranging in size from molecules to micron or larger microcrystals, and even foreign particles were visually recorded. From these observations and measurements a more complete understanding of the detailed character of macromolecular crystals is emerging, one that reveals levels of complexity previously unsuspected. The features of these crystals apparent in AFM images undoubtedly influence the diffraction properties of the crystals and the quality of the images obtained by X-ray crystallography.