Atomic force microscopy applications in macromolecular crystallography

Atomic force microscopy (AFM) can be applied both in situ and ex situ to st udy the growth of crystals from solution. The method is particularly useful for investigating the crystallization of proteins, nucleic acids and virus es because it can be carried out in the mother liquor and in a non-perturbi ng fashion. Interactions and transformations between various growth mechani sms can be directly visualized as a function of supersaturation, as can the incorporation of diverse impurities and the formation and propagation of d efects. Because the crystals can be observed over long periods, it is also possible to obtain precise quantitative measures of the kinetic parameters for nucleation and growth. Finally, AFM has allowed us to identify a number of previously unsuspected phenomena that influence nucleation, rate of gro wth and the ultimate perfection of macromolecular crystals. These are all f eatures which are important in determining the ultimate resolution and qual ity of a crystal's diffraction pattern.