Atomic force microscopy in the study of macromolecular crystal growth

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 se quential AFM images taken at brief intervals over many hours, or even days, the mechanisms and kinetics of the growth process can be defined. the appe arance of both two- and three-dimensional nuclei on crystal surfaces have b een visualized, defect structures of crystals were clearly evident, and def ect densities of crystals were also determined. The incorporation of a wide range of impurities, ranging in size from molecules to microns or larger m icrocrystals, and even foreign particles were visually recorded. From these observations and measurements, a more complex understanding of the detaile d character of macromolecular crystals is emerging, one that reveals levels of complexity previously unsuspected. The unique features of these crystal s, apparently in AFM images, undoubtedly influence the diffraction properti es of the crystals and the quality of the molecular images obtained by X-ra y crystallography.