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Understanding amyloid aggregation by statistical analysis of atomic force microscopy images

Nature Nanotechnology volume 5, pages 423–428 (2010)Cite this article

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Abstract

The aggregation of proteins is central to many aspects of daily life, including food processing, blood coagulation, eye cataract formation disease and prion-related neurodegenerative infections1,2,3,4,5. However, the physical mechanisms responsible for amyloidosis—the irreversible fibril formation of various proteins that is linked to disorders such as Alzheimer's, Creutzfeldt–Jakob and Huntington's diseases—have not yet been fully elucidated6,7,8,9. Here, we show that different stages of amyloid aggregation can be examined by performing a statistical polymer physics analysis of single-molecule atomic force microscopy images of heat-denatured β-lactoglobulin fibrils. The atomic force microscopy analysis, supported by theoretical arguments, reveals that the fibrils have a multistranded helical shape with twisted ribbon-like structures. Our results also indicate a possible general model for amyloid fibril assembly and illustrate the potential of this approach for investigating fibrillar systems.

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Figure 1: AFM imaging, contour length and maximum height distribution of β-lactoglobulin fibrils.
Figure 2: AFM imaging of fibril splitting and thinning.
Figure 3: Different periods of β-lactoglobulin fibrils.
Figure 4: Linear relation between the number of filaments and persistence length and periodicity of β-lactoglobulin fibrils.

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Acknowledgements

The authors thank G. Witz and J. Vieira for helpful discussions and assistance during the experiments.

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Authors and Affiliations

  1. Laboratoire de Physique de la Matière Vivante, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland

    Jozef Adamcik & Giovanni Dietler

  2. Department of Physics and Fribourg Center for Nanomaterials, University of Fribourg, Ch. Musée 3, Fribourg, CH-1700, Switzerland

    Jin-Mi Jung

  3. Laboratoire de Biophysique Statistique, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland

    Jérôme Flakowski & Paolo De Los Rios

  4. ETH Zurich, Food & Soft Materials Science, Institute of Food, Nutrition & Health, LFO23, Schmelzbergstrasse 9, Zürich, 8092, Switzerland

    Raffaele Mezzenga

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  1. Jozef Adamcik
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  4. Paolo De Los Rios
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  6. Raffaele Mezzenga
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Contributions

J.A. performed AFM imaging, analysed data and wrote the paper. J.M.J. prepared the fibrils. J.F. ran coarse-grain molecular dynamics simulations of the fibrils and analysed data. P.D.L.R and G.D. analysed data and wrote the paper. R.M designed the study, analysed the data and wrote the paper. All authors discussed the results and commented on the manuscript.

Corresponding authors

Correspondence to Giovanni Dietler or Raffaele Mezzenga.

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The authors declare no competing financial interests.

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Adamcik, J., Jung, JM., Flakowski, J. et al. Understanding amyloid aggregation by statistical analysis of atomic force microscopy images. Nature Nanotech 5, 423–428 (2010). https://doi.org/10.1038/nnano.2010.59

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