Flash frozen under the electron microscope: Examining the mechanical properties of Alzheimer鈥檚 amyloid fibrils
(糖心视频Org.com) -- Alzheimer鈥檚 disease, Parkinson鈥檚 disease, type-II diabetes, and prion diseases like BSE all involve the deposition of amyloid fibrils in tissues and organs. These are fibrous clumps of incorrectly folded proteins; their exact structures and their roles in pathological processes are not yet completely understood.
By using electron microscopic images of flash frozen samples, researchers have now been able to examine the exact structure of Alzheimer鈥檚 amyloid fibrils and to assess their mechanical properties. As the team reports in the journal Angewandte Chemie, the fibrils are very stiff -- one of the underlying causes of their pathogenicity.
Because amyloid fibrils are very difficult to analyze with traditional biophysical techniques, Marcus F盲ndrich (Max Planck Unit for Enzymology of Protein Folding, Halle/Saale, Germany), Carsten Sachse (MRC Laboratory of Molecular Biology, Cambridge, UK), and Nikolaus Grigorieff (Brandeis University, Waltham, USA) were forced to take another approach: They examined Alzheimer鈥檚 amyloid fibrils by electron cryomicroscopy. 鈥淭hese experiments allowed us to examine the structure of the fibrils at a previously unattainable resolution,鈥� explains F盲ndrich.
The fibrils appear in twisted bands about 20 nm wide and are often bent in the raw electron microscopic images. 鈥淭hese bent fibrils are a snapshot of the fibrils in solution,鈥� says F盲ndrich. 鈥淲e use the degree of bending and twisting to calculate how stiff the fibrils are.鈥� This revealed that the Alzheimer鈥檚 amyloid fibrils are relatively rigid structures. 鈥淭he uncontrolled formation of such stiff fibrils is presumably critical for the pathogenicity of amyloid fibrils,鈥� reports F盲ndrich. 鈥淚n many amyloid diseases, the fibrils are preferentially deposited in tissues that are normally contractile or elastic, like the heart muscle or the walls of blood vessels. Medical findings indicate that the fibrils somewhat stiffen these tissues.鈥�
鈥淚n addition, our data may help to better evaluate the possible uses of amyloid fibers as novel biotechnological agents,鈥� reports F盲ndrich. Based on their material properties and ease of modification, amyloid fibers are potentially interesting as novel building materials.
More information: Marcus F盲ndrich, Nanoscale Flexibility Parameters of Alzheimer Amyloid Fibrils Determined by Electron Cryo-Microscopy, Angewandte Chemie International Edition 2010, 49, No. 7, Permalink:
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