The atomic force microscope (AFM) allows biomolecules to be observed andmanipulated under native conditions. It produces images with an outstanding signal-to-noiseratio and addresses single molecules while the sample is in a buffer solution. Progress insample preparation and instrumentation has led to topographs that reveal subnanometerdetails and the surface dynamics of biomolecules.Tethering single molecules between asupport and a retracting AFM tip produces force-extension curves, giving informationabout the mechanical stability of secondary structural elements. For both imaging andforce spectroscopy, the cantilever and its tip are critical: the mechanical properties of thecantilever dictate the force sensitivity and the scanning speed, whereas the tip shapedetermines the achievable lateral resolution.

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