Nano-mechanical characterization of disassembling amyloid fibrils using the Peak Force QNM method

Biopolymers. 2017 Feb;107(2):61-69. doi: 10.1002/bip.22992.

Abstract

The comprehensive understanding of disassembly mechanism of amyloid fibrils requires nano-scale characterization of the mechanical properties of amyloid fibrils during the disassembly process. In this work, gemini surfactant C12 C6 C12 Br2 micelles were used as a probe to disassemble Aβ(1-40) fibrils. The microstructure evolution and nano-mechanical properties of Aβ(1-40) fibrils during the disassembly process were systematically investigated by the Peak Force Quantitative Nano-mechanical (PF-QNM) technique. The results show an obvious decrease in Young's modulus of mature fibrils with high β-sheet contents (2.4 ± 1.0 GPa) in comparison to the resulting peptide/surfactant complexes (1.1 ± 0.8 GPa) with loose surface structures. Interestingly, the Young's modulus of spherical peptide/surfactant complexes on the core was more than 3 GPa. This strategy can be used as a standard protocol to investigate the interaction mechanism between amyloid fibrils and small molecules, which may open up new possibilities to explore the mechanism of relevant human diseases.

Keywords: Peak Force QNM; amyloid fibrils; disassembly mechanism; nano-mechanical properties.

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism*
  • Elastic Modulus
  • Humans
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Nanotechnology
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Surface-Active Agents / chemistry
  • Surface-Active Agents / metabolism

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments
  • Surface-Active Agents
  • amyloid beta-protein (1-40)