The atomic force microscope (AFM) allows biomolecules to be observed and manipulated under native conditions. It produces images with an outstanding signal-to-noise ratio and addresses single molecules while the sample is in a buffer solution. Progress in sample preparation and instrumentation has led to topographs that reveal subnanometer details and the surface dynamics of biomolecules. Tethering single molecules between a support and a retracting AFM tip produces force–extension curves, giving information about the mechanical stability of secondary structural elements. For both imaging and force spectroscopy, the cantilever and its tip are critical:the mechanical properties of the cantilever dictate the force sensitivity and the scanning speed, whereas the tip shape determines the achievable lateral resolution.
