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

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.