In situ monitoring the aggregation dynamics of amyloid-β protein Aβ42 in physiological media via a raman-based frequency shift method

Wenfeng Zhu, Yibing Wang, Dan Xie, Linxiu Cheng, Ping Wang, Qingdao Zeng, Min Li, Yuliang Zhao

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Amyloid-β protein (Aβ) is a major biomarker candidate for the diagnosis of Alzheimer's disease (AD). It is known that the core segment of Aβ42 tends to aggregate into neurotoxic soluble oligomeric species and finally into fibrillar structures associated with AD; however, much remains to be learned about the conformational changes and dynamic aggregation processes of Aβ protein in solution. Herein we exploit the selectivity of affinity peptides, singled out by biopanning a phage display library, to recognize and capture Aβ42 and its fibers. The sensitivity of surface-enhanced Raman spectroscopy (SERS) to subtle electronic changes of a Raman reporter upon Aβ42 binding, that is, the frequency shift SERS assay, is employed to develop a reliable sensor for both in situ Aβ42 aggregation monitoring and Aβ42 monomers and fibers detection. Atomic force microscope (AFM) imaging is used to investigate the dynamic aggregation processes of Aβ42 on mica and confirms the conclusions of the SERS studies. Finally sensing of Aβ42 and its fibers in fetal bovine serum (FBS) solution is shown to have a limit of detection of ~10-9 mol/L.

Original languageEnglish (US)
Pages (from-to)814-824
Number of pages11
JournalACS Applied Bio Materials
Volume1
Issue number3
DOIs
StatePublished - Sep 17 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the National Natural Science Foundation of China (31671012) and the National Basic Research Program of China (2015CB932004). Y.-B.W. is thankful for the support from Mr. Shaolei Wang and the Research Center of Analysis and Test of ECUST.

Publisher Copyright:
© 2018 American Chemical Society.

Keywords

  • Aggregation process
  • Alzheimer's disease
  • Aβ42
  • Frequency shift biosensing
  • SERS

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