Biological cryo atomic force microscopy: a brief review.

Despite many successes, atomic force microscopy (AFM) of biological specimens at room temperature is still severely limited by at least two factors: the softness and the thermal motion of flexible multi-domain/subunit molecules. Both problems can be overcome by imaging biological structures at cryogenic temperatures. Even though the instrumentation is considerably more complex and earlier attempts were largely unsuccessful, cryo-AFM has recently been demonstrated on a number of biological specimens, using an AFM operated in liquid nitrogen vapor under ambient pressure. In this brief review, both the method of instrumentation and the latest biological applications are discussed. Not only has the cryo-AFM attained high resolution on those specimens that could not be well imaged at room temperature, but it has also produced potentially important information on several specimens. These results firmly establish the cryo-AFM as a useful and versatile structural probe in biology with its own unique capabilities.