Structure by Feel

Applying the sensitive touch of atomic force microscopy to DNA, cells, and proteins

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A TOUCHING SIGHT: The tip of an atomic force microscope probe is so small that it allows researchers to topographically map unaltered macromolecules and cells or measure the mechanical properties of biological samples. © MATTHIAS KULKA/CORBISEven powerful light microscopes fail scientists when molecules measure less than 200 nanometers, roughly a thousandth the diameter of an eyelash. However, touch can get a good bit closer than sight. By tapping and stretching molecules as small as a single nanometer, atomic force microscopes (AFM) reveal the topography and mechanical properties of objects or features too small for light or electron microscopes to discriminate.

In contrast to both light and scanning electron microscopy, for AFM the sample need not be dehydrated, labeled with fluorescent tags, or coated in metal before imaging. Therefore, cells, proteins, and DNA can be imaged unaltered. These qualities have won the instrument enthusiastic fans. “AFM is the simplest, most reliable, resilient, and powerful instrument I have ever come across,” says Julio Fernandez, a biophysicist at Columbia University in New York City. “It is spectacularly counterintuitive, because it looks so simple but produces such magnificent science.”

Physicists invented AFM in 1986 as a technique to assess the properties of inorganic matter at the nanoscale. As these tools catch on among cell biologists, commercial manufacturers have begun developing and marketing them to suit biological-science needs, which reduces ...

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