Imaging and Interrogating Native Membrane Proteins Using the Atomic Force Microscope

Membrane proteins exist in a lipid bilayer and provide for cell–cell communication, transport solutes, and convert energies. Detergents are used to extract membrane proteins and keep them in solution for purification and subsequent analyses. The atomic force microscope (AFM) is a powerful tool for imaging and manipulating membrane proteins in their native state without the necessity to solubilize them. It allows membranes that are adsorbed to flat solid supports to be raster-scanned in physiological solutions with an atomically sharp tip. Therefore, AFM is capable of observing biological molecular machines at work. Superb images of native membranes have been recorded, and a quantitative interpretation of the data acquired using the AFM tip has become possible. In addition, multifunctional probes to simultaneously acquire information on the topography and electrical properties of membrane proteins have been produced. This progress is discussed here and fosters expectations for future developments and applications of AFM and single-molecule force spectroscopy.