Understanding amyloid aggregation by statistical analysis of atomic force microscopy images

Nat Nanotechnol. 2010 Jun;5(6):423-8. doi: 10.1038/nnano.2010.59. Epub 2010 Apr 11.

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 infections. 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 elucidated. 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 beta-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.

MeSH terms

  • Amyloid / chemistry
  • Amyloid / ultrastructure*
  • Animals
  • Cattle
  • Lactoglobulins / chemistry
  • Lactoglobulins / ultrastructure
  • Microscopy, Atomic Force / methods*
  • Models, Statistical
  • Nanostructures / chemistry
  • Nanostructures / ultrastructure*
  • Protein Denaturation
  • Protein Multimerization

Substances

  • Amyloid
  • Lactoglobulins