Characterization of Protein–Protein Interactions Using Atomic Force Microscopy

Atomic force microscopy (AFM), invented in 1986, expanded the application of scanning tunneling microscopy to nonconductive, soft, and live biological samples (Binnig et al., 1986; Hansma et al., 1988; Marti et al., 1988; Drake et al., 1989). AFM has several capabilities, including characterizing topographic details of surfaces from the submolecular level to the cellular level (Radmacher et al., 1992), and monitoring the dynamic process of single molecules in physiological relevant solutions (Drake et al., 1989; Engel and Muller, 2000). More excitingly, AFM not only extends our ‘‘vision,’’ but also extends our ability to ‘‘touch and manipulate’’ during our exploration of the biological system at the molecular level. For example, AFM can be used to manipulate macromolecules (Zlatanova and Leuba, 2003; Bockelmann, 2004; Gutsmann et al., 2004), monitor the unfolding of proteins, RNA, and protein fibers (Carrion-Vazquez et al., 1999; Fisher et al., 2000; Zhuang and Rief, 2003; Rounsevell et al., 2004), and measure the forces between interacting molecules (Chilkoti et al., 1995; Dammer et al., 1995; Ros et al., 2004). Over the past two decades, the application of AFM has advanced our knowledge in many areas of the biological sciences including DNA (Fritzsche et al., 1997; Hansma, 2001; Hansma Schuck / Protein Interactions chap02 Final Proof page 39 22.12.2006 10:51am