Characterizing individual protein aggregates by infrared nanospectroscopy and atomic force microscopy

Francesco Simone Ruggeri*, Tomas Šneideris, Sean Chia, Michele Vendruscolo, Tuomas P.J. Knowles

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

Abstract

The phenomenon of protein misfolding and aggregation results in the formation of highly heterogeneous protein aggregates, which are associated with neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. In particular low molecular weight aggregates, amyloid oligomers, have been shown to possess generic cytotoxic properties and are implicated as neurotoxins in many forms of dementia. We illustrate the use of methods based on atomic force microscopy (AFM) to address the challenging task of characterizing the morphological, structural and chemical properties of these aggregates, which are difficult to study using conventional structural methods or bulk biophysical methods because of their heterogeneity and transient nature. Scanning probe microscopy approaches are now capable of investigating the morphology of amyloid aggregates with sub-nanometer resolution. We show here that infrared (IR) nanospectroscopy (AFM-IR), which simultaneously exploits the high resolution of AFM and the chemical recognition power of IR spectroscopy, can go further and enable the characterization of the structural properties of individual protein aggregates, and thus offer insights into the aggregation mechanisms. Since the approach that we describe can be applied also to the investigations of the interactions of protein assemblies with small molecules and antibodies, it can deliver fundamental information to develop new therapeutic compounds to diagnose or treat neurodegenerative disorders.

Original languageEnglish
Article numbere60108
JournalJournal of Visualized Experiments
Volume2019
Issue number151
DOIs
Publication statusPublished - 2019
Externally publishedYes

Keywords

  • Amyloid
  • Atomic force microscopy
  • Biochemistry
  • Infrared nanospectroscopy
  • Issue 151
  • Neurodegeneration
  • Protein aggregation
  • Single molecule analysis
  • Spectroscopy

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