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.