AFM Analyses of Mitochondria: Genome Structure and Dynamics in Living Cell

Molecular imaging at nano-meter scale in millisecond time region and force measurement at pico-Newton level are indispensable for understanding of the action mechanisms of biological macromolecules. Techniques and devices of atomic force microscopy (AFM) have been developed over the last three decades and now fulfill such requirements [1-3]. We have been using these techniques and successful in (i) application of high-speed AFM to DNA-protein interactions, (ii) capturing the motion of membrane proteins at work, and (iii) visual analyses of live cell and intracellular organella using a high-speed AFM combined with inverted fluorescent microscopy (FM). High-speed AFM equipped with an optical/fluorescence detection device has been a long-standing wish. Now our newly developed hybrid AFM-FM [4] is powerful tool for investigating cellular morphologies and events towards the elucidation of dynamic structure-function relationships of biological macromolecules on live cell membrane. This instrument also made it possible to monitor cytoskeletal and mitochondrial membrane dynamics by probing from outside the cells.