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Asymmetric amyloid fibril elongation: A new perspective on a symmetric world

Authors

  • Caryn L. Heldt,

    1. Howard P. Isermann Department of Chemical and Biological Engineering and The Center of Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180-3590
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    • Current Adress: Department of Chemical Engineering, Michigan Technological University, 1400 Townsend Drive, Houghton, MI 49931

  • Shuqi Zhang,

    1. Howard P. Isermann Department of Chemical and Biological Engineering and The Center of Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180-3590
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  • Georges Belfort

    Corresponding author
    1. Howard P. Isermann Department of Chemical and Biological Engineering and The Center of Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York 12180-3590
    • 110 8th Street, Troy, NY 12180
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Abstract

Amyloids are insoluble, fibrous proteins formed through the aggregation of misfolded proteins. They accumulate in the tissue of individuals with degenerative diseases, such as Parkinson's and Alzheimer's. The purpose of this study was to determine whether fibril growth from an initial model fibril seed is unidirectional or bidirectional. The prevailing theory on amyloid formation is that a symmetric fibril elongates equally from both ends. This study provides evidence to the contrary; the process occurs predominately unidirectionally, demonstrating that amyloid fibrils may be asymmetric and propagate mostly in one direction. Alexa Fluor 568 labeled insulin fibrils were seeded into a native insulin solution and allowed to elongate at 65°C while the kinetics of fibril growth was monitored. The resulting elongated fibrils were labeled with thioflavin-T, and the fluorescent images of the fibrils show that a majority of the elongated fibrils propagated along only one end of the seed, with the remaining labeled fibrils having bidirectional elongation or no elongation. Using a crystallographic model, we offer a structural explanation for asymmetric growth of the insulin fibrils. Thus, instead of the current view that fibrils grow symmetrically from both ends of the fibril, this is the first evidence that insulin amyloid fibrils formed in solution are asymmetric and appear to grow from only one end. Proteins 2010. © 2010 Wiley-Liss, Inc.

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