Single-molecule atomic force microscopy force spectroscopy study of Aβ-40 interactions

Bo Hyun Kim, Nicholas Y. Palermo, Sándor Lovas, Tatiana Zaikova, John F W Keana, Yuri L. Lyubchenko

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Misfolding and aggregation of amyloid β-40 (Aβ-40) peptide play key roles in the development of Alzheimer's disease (AD). However, very little is known about the molecular mechanisms underlying these molecular processes. We developed a novel experimental approach that can directly probe aggregation-prone states of proteins and their interactions. In this approach, the proteins are anchored to the surface of the atomic force microscopy substrate (mica) and the probe, and the interaction between anchored molecules is measured in the approach-retraction cycles. We used dynamic force spectroscopy (DFS) to measure the stability of transiently formed dimers. One of the major findings from DFS analysis of α-synuclein (α-Syn) is that dimeric complexes formed by misfolded α-Syn protein are very stable and dissociate over a range of seconds. This differs markedly from the dynamics of monomers, which occurs on a microsecond to nanosecond time scale. Here we applied the same approach to quantitatively characterize interactions of Aβ-40 peptides over a broad range of pH values. These studies showed that misfolded dimers are characterized by lifetimes in the range of seconds. This value depends on pH and varies between 2.7 s for pH 2.7 and 0.1 s for pH 7, indicating that the aggregation properties of Aβ-40 are modulated by the environmental conditions. The analysis of the contour lengths revealed the existence of various pathways for dimer dissociation, suggesting that dimers with different conformations are formed. These structural variations result in different aggregation pathways, leading to different types of oligomers and higher-order aggregates, including fibrils.

Original languageEnglish
Pages (from-to)5154-5162
Number of pages9
JournalBiochemistry
Volume50
Issue number23
DOIs
StatePublished - Jun 14 2011

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Atomic Force Microscopy
Dimers
Atomic force microscopy
Spectrum Analysis
Agglomeration
Spectroscopy
Molecules
Synucleins
Dissociative Disorders
Peptides
Proteins
Oligomers
Amyloid
Conformations
Alzheimer Disease
Monomers
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Kim, B. H., Palermo, N. Y., Lovas, S., Zaikova, T., Keana, J. F. W., & Lyubchenko, Y. L. (2011). Single-molecule atomic force microscopy force spectroscopy study of Aβ-40 interactions. Biochemistry, 50(23), 5154-5162. https://doi.org/10.1021/bi200147a

Single-molecule atomic force microscopy force spectroscopy study of Aβ-40 interactions. / Kim, Bo Hyun; Palermo, Nicholas Y.; Lovas, Sándor; Zaikova, Tatiana; Keana, John F W; Lyubchenko, Yuri L.

In: Biochemistry, Vol. 50, No. 23, 14.06.2011, p. 5154-5162.

Research output: Contribution to journalArticle

Kim, BH, Palermo, NY, Lovas, S, Zaikova, T, Keana, JFW & Lyubchenko, YL 2011, 'Single-molecule atomic force microscopy force spectroscopy study of Aβ-40 interactions', Biochemistry, vol. 50, no. 23, pp. 5154-5162. https://doi.org/10.1021/bi200147a
Kim, Bo Hyun ; Palermo, Nicholas Y. ; Lovas, Sándor ; Zaikova, Tatiana ; Keana, John F W ; Lyubchenko, Yuri L. / Single-molecule atomic force microscopy force spectroscopy study of Aβ-40 interactions. In: Biochemistry. 2011 ; Vol. 50, No. 23. pp. 5154-5162.
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