Tiny levers map protein surfaces

March 18, 2004
Researchers at Carnegie Mellon University are using atomic force microscopy (AFM) to illuminate molecular scale processes underlying Alzheimer's disease. The instruments look at insoluble plaques associated with the disease and may lead to new diagnostics and treatments.

In using AFM, a tiny lever with an ultrasharp tip is scanned across a surface from side-to-side and top-to-bottom, similar to a cursor moving across a computer screen. A laser beam reflected from the lever's end monitors its vertical motion. Disturbance of the lever motion by nanoscale features on the sample's surface is used to reconstruct a 3D map of the surface. Researchers use custom-written software to process and analyze AFM images.

"AFM provides three-dimensional topographical information at the nanoscale, which makes it important in assessing how molecules like antibodies effectively inhibit protein aggregation associated with Alzheimer's," says Tomasz Kowalewski, Ph.D., assistant professor of chemistry. Alzheimer's belongs to a class of disorders called conformational diseases, which are caused by changes in a protein's physical state. "Because AFM probes the physical state of proteins, it could really help understand conformational diseases, which traditionally have been difficult to fight," adds Kowalewski.

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