IMAGING BIOLOGICAL STRUCTURES WITH THE CRYO ATOMIC-FORCE MICROSCOPE

It has long been recognized that one of the major limitations in biolo gical atomic force microscopy (AFM) is the softness of most biological samples, which are easily deformed or damaged by the AFM tip, because of the high pressure in the contact area, especially from the very sh arp tips required for high resolution. Another is the molecular motion present at room temperature due to thermal fluctuation. Using an AFM operated in liquid nitrogen vapor (cryo-AFM), we demonstrate that cryo -AFM can be applied to a large variety of biological samples, from imm unoglobulins to DNA to cell surfaces. The resolution achieved with cry o-AFM is much improved when compared with AFM al room temperature with similar specimens, and is comparable to that of cryo-electron microsc opy on randomly oriented macromolecules. We will also discuss the tech nical problems that remain to be solved for achieving even higher reso lution with cryo-AFM and other possible applications of this novel tec hnique.