Probing the role of metal cations on the aggregation behavior of amyloid β-peptide at a single molecule level by AFM
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With the development of nanotechnology, understanding of intermolecular interactions on a single molecule level by atomic force spectroscopy (AFM) has played an important role in molecular biology and biomedical science. In recent years, some research suggested that the presence of metal cations is an important regulator in the processes of misfolding and aggregation of the amyloid β-protein (Aβ), which may be an important etiological factor of Alzheimer’s disease. However, the knowledge on the principle of interactions between Aβ and metal cations at the single molecule level is still poor understood. In this paper, the amyloid β-protein (Aβ) was fabricated on substrate of mixed thiol-modified gold nanoparticles using self-assembled monolayer method and the adhesion force in the longitudinal direction between metal cations and Aβ42 were investigated by AFM. The role of metal ions on Aβ aggregation is discussed from the perspective of single molecular force. The force results showed that the specific adhesion force F i and the nonspecific force F 0 between a single Aβ–Aβ pair in control experiment were calculated as 42 ± 3 and 80 pN, respectively. However, F i between a single Aβ–Aβ pair in the presence of Cu2+, Zn2+, Ca2+ and Al3+ increased dramatically to 84 ± 6, 89 ± 3, 73 ± 5, 95 ± 5 pN successively, which indicated that unbinding between Aβ proteins is accelerated in the presence of metal cations. What is more, the imaging results showed that substoichiometric copper cations accelerate the formation of fibrils within 3 days. The combined atomic force spectroscopy and imaging analysis indicate that metal cations play a role in promoting the aggregating behavior of Aβ42.
KeywordsNanotechnology Atomic force microscopy (AFM) Interactions Metal cations Amyloid β-protein Nanoparticles Biomedicine
This work was supported by the Foundation and Advanced Research Project of CQ CSTC (2013jjB0011), and Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province.
- Burdick D, Soreghan B, Kwon M, Kosmoski J, Knauder M, Henschen A, Yates J, Cotman C, Glabe C (1992) Assembly and aggregation properties of synthetic alzheimer’s A4/beta amyloid peptide analogs. J Biol Chem 267:546–554Google Scholar
- Wiltfang J, Esselmann H, Bibl M, Huell M, Hampel H, Kessler H, Froelich L, Schroeder J, Peters O, Jessen F, Luckhaus C, Perneczky R, Jahn H, Fiszer M, Maler JM, Zimmermann R, Bruckmoser R, Kornhuber J, Lewczuk P (2007) Amyloid beta peptide ratio 42/40 but not A beta 42 correlates with phospho-Tau in patients with low- and high-CSF A beta 40 load. J Neurochem 101:1053–1059CrossRefGoogle Scholar