High-speed AFM imaging.

Proteins are dynamic in nature and function at the single molecule level. To achieve a straightforward and in-depth understanding of their underlying functional mechanism, we need to directly observe protein molecules at work at high resolution, without the use of protein-attached markers. To realize such objectives, high-speed atomic force microscopy (HS-AFM) has been developed and recently its capability has been fully established. This approach opens a new avenue to directly and closely observe individual molecules at submolecular spatial resolution and sub-100 ms time resolution. The captured molecular movies of proteins directly report and provide great insights into how the proteins function. Moreover, the very recent progress of HS-AFM technology has extended its use to the observation of dynamic cellular processes. In this article, I review imaging studies to show the innovative power and potential of this new microscopy.