Nanoprobing of misfolding and interactions of amyloid β 42 protein

Bo Hyun Kim, Yuri L Lyubchenko

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The assembly of amyloid β (Aβ) proteins into nanostructures is currently considered a major pathway of Alzheimer's disease development, but the molecular mechanisms of this self-assembly process remains unclear. Recently, we showed that single-molecule AFM force spectroscopy (SMFS) is capable of probing the dynamics and interaction between Aβ40 peptides, and these studies allowed us to shed new light on transiently existing Aβ40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of Aβ42 peptide, the most toxic Aβ alloform. The quantitative analysis of SMFS data demonstrated that Aβ interaction leads to the formation of dimers with a lifetime in the range of a second. Interaction via C-terminal segments prevailed at pH 7, but interaction within the peptide center prevailed at acidic pH levels. The difference in the misfolding properties for Aβ40 and Aβ42 peptides and the mechanisms of amyloid nanoassembly are discussed. From the Clinical Editor: Despite decades of intense research, Alzheimer's disease still remains incurable. This novel study focuses on the assembly of amyloid β proteins into nanostructures, which is a key mechanism in Alzheimer's disease development. Single molecule atomic force spectroscopy is utilized to shed light on the molecular mechanisms of this self-assembly process.

Original languageEnglish (US)
Pages (from-to)871-878
Number of pages8
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number4
DOIs
StatePublished - May 2014

Fingerprint

Amyloidogenic Proteins
Peptides
Spectrum Analysis
Spectroscopy
Alzheimer Disease
Molecules
Nanostructures
Self assembly
Serum Amyloid A Protein
Poisons
Amyloid
Dimers
Proteins
Chemical analysis
Research
peptide A42

Keywords

  • Amyloid beta
  • Contour length
  • Dimerization pathways
  • Misfolding
  • Single-molecule force spectroscopy

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Nanoprobing of misfolding and interactions of amyloid β 42 protein. / Kim, Bo Hyun; Lyubchenko, Yuri L.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 10, No. 4, 05.2014, p. 871-878.

Research output: Contribution to journalArticle

@article{ea39d6a439124310b920dbfaafba6e95,
title = "Nanoprobing of misfolding and interactions of amyloid β 42 protein",
abstract = "The assembly of amyloid β (Aβ) proteins into nanostructures is currently considered a major pathway of Alzheimer's disease development, but the molecular mechanisms of this self-assembly process remains unclear. Recently, we showed that single-molecule AFM force spectroscopy (SMFS) is capable of probing the dynamics and interaction between Aβ40 peptides, and these studies allowed us to shed new light on transiently existing Aβ40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of Aβ42 peptide, the most toxic Aβ alloform. The quantitative analysis of SMFS data demonstrated that Aβ interaction leads to the formation of dimers with a lifetime in the range of a second. Interaction via C-terminal segments prevailed at pH 7, but interaction within the peptide center prevailed at acidic pH levels. The difference in the misfolding properties for Aβ40 and Aβ42 peptides and the mechanisms of amyloid nanoassembly are discussed. From the Clinical Editor: Despite decades of intense research, Alzheimer's disease still remains incurable. This novel study focuses on the assembly of amyloid β proteins into nanostructures, which is a key mechanism in Alzheimer's disease development. Single molecule atomic force spectroscopy is utilized to shed light on the molecular mechanisms of this self-assembly process.",
keywords = "Amyloid beta, Contour length, Dimerization pathways, Misfolding, Single-molecule force spectroscopy",
author = "Kim, {Bo Hyun} and Lyubchenko, {Yuri L}",
year = "2014",
month = "5",
doi = "10.1016/j.nano.2013.11.016",
language = "English (US)",
volume = "10",
pages = "871--878",
journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",
issn = "1549-9634",
publisher = "Elsevier Inc.",
number = "4",

}

TY - JOUR

T1 - Nanoprobing of misfolding and interactions of amyloid β 42 protein

AU - Kim, Bo Hyun

AU - Lyubchenko, Yuri L

PY - 2014/5

Y1 - 2014/5

N2 - The assembly of amyloid β (Aβ) proteins into nanostructures is currently considered a major pathway of Alzheimer's disease development, but the molecular mechanisms of this self-assembly process remains unclear. Recently, we showed that single-molecule AFM force spectroscopy (SMFS) is capable of probing the dynamics and interaction between Aβ40 peptides, and these studies allowed us to shed new light on transiently existing Aβ40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of Aβ42 peptide, the most toxic Aβ alloform. The quantitative analysis of SMFS data demonstrated that Aβ interaction leads to the formation of dimers with a lifetime in the range of a second. Interaction via C-terminal segments prevailed at pH 7, but interaction within the peptide center prevailed at acidic pH levels. The difference in the misfolding properties for Aβ40 and Aβ42 peptides and the mechanisms of amyloid nanoassembly are discussed. From the Clinical Editor: Despite decades of intense research, Alzheimer's disease still remains incurable. This novel study focuses on the assembly of amyloid β proteins into nanostructures, which is a key mechanism in Alzheimer's disease development. Single molecule atomic force spectroscopy is utilized to shed light on the molecular mechanisms of this self-assembly process.

AB - The assembly of amyloid β (Aβ) proteins into nanostructures is currently considered a major pathway of Alzheimer's disease development, but the molecular mechanisms of this self-assembly process remains unclear. Recently, we showed that single-molecule AFM force spectroscopy (SMFS) is capable of probing the dynamics and interaction between Aβ40 peptides, and these studies allowed us to shed new light on transiently existing Aβ40 misfolding states. In this study, we applied the same SMFS approach to characterize the misfolding of Aβ42 peptide, the most toxic Aβ alloform. The quantitative analysis of SMFS data demonstrated that Aβ interaction leads to the formation of dimers with a lifetime in the range of a second. Interaction via C-terminal segments prevailed at pH 7, but interaction within the peptide center prevailed at acidic pH levels. The difference in the misfolding properties for Aβ40 and Aβ42 peptides and the mechanisms of amyloid nanoassembly are discussed. From the Clinical Editor: Despite decades of intense research, Alzheimer's disease still remains incurable. This novel study focuses on the assembly of amyloid β proteins into nanostructures, which is a key mechanism in Alzheimer's disease development. Single molecule atomic force spectroscopy is utilized to shed light on the molecular mechanisms of this self-assembly process.

KW - Amyloid beta

KW - Contour length

KW - Dimerization pathways

KW - Misfolding

KW - Single-molecule force spectroscopy

UR - http://www.scopus.com/inward/record.url?scp=84900309223&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900309223&partnerID=8YFLogxK

U2 - 10.1016/j.nano.2013.11.016

DO - 10.1016/j.nano.2013.11.016

M3 - Article

C2 - 24333588

AN - SCOPUS:84900309223

VL - 10

SP - 871

EP - 878

JO - Nanomedicine: Nanotechnology, Biology, and Medicine

JF - Nanomedicine: Nanotechnology, Biology, and Medicine

SN - 1549-9634

IS - 4

ER -