Biophysical Reviews

, Volume 10, Issue 4, pp 1133–1149 | Cite as

Understanding amyloid fibril formation using protein fragments: structural investigations via vibrational spectroscopy and solid-state NMR

  • Benjamin Martial
  • Thierry Lefèvre
  • Michèle AugerEmail author


It is well established that amyloid proteins play a primary role in neurodegenerative diseases. Alzheimer’s, Parkinson’s, type II diabetes, and Creutzfeldt-Jakob’s diseases are part of a wider family encompassing more than 50 human pathologies related to aggregation of proteins. Although this field of research is thoroughly investigated, several aspects of fibrillization remain misunderstood, which in turn slows down, or even impedes, advances in treating and curing amyloidoses. To solve this problem, several research groups have chosen to focus on short fragments of amyloid proteins, sequences that have been found to be of great importance for the amyloid formation process. Studying short peptides allows bypassing the complexity of working with full-length proteins and may provide important information relative to critical segments of amyloid proteins. To this end, efficient biophysical tools are required. In this review, we focus on two essential types of spectroscopic techniques, i.e., vibrational spectroscopy and its derivatives (conventional Raman scattering, deep-UV resonance Raman (DUVRR), Raman optical activity (ROA), surface-enhanced Raman spectroscopy (SERS), tip-enhanced Raman spectroscopy (TERS), infrared (IR) absorption spectroscopy, vibrational circular dichroism (VCD)) and solid-state nuclear magnetic resonance (ssNMR). These techniques revealed powerful to provide a better atomic and molecular comprehension of the amyloidogenic process and fibril structure. This review aims at underlining the information that these techniques can provide and at highlighting their strengths and weaknesses when studying amyloid fragments. Meaningful examples from the literature are provided for each technique, and their complementarity is stressed for the kinetic and structural characterization of amyloid fibril formation.


Amyloid fragments Raman spectroscopy IR spectroscopy VCD spectroscopy ssNMR Polymorphism 



Two-dimensional infrared


Three-dimensional z-filtered transferred-echo double-resonance




Alzheimer’s disease


Atomic force microscopy




Attenuated total reflection infrared



Cryo-electron microscopy


Chemical shift anisotropy


Dipolar-assisted rotational resonance


Density functional theory


Dynamic nuclear polarization


Double-quantum filtered dipolar recoupling in a windowless sequence


Dipolar recoupling in a windowless sequence


Deep-UV resonance Raman


Huntington’s disease


Islet amyloid polypeptide




Magic-angle spinning


Parkinson’s disease


Constant-time recoupling with π-pulses lasting one-third of the MAS rotation period




Polyproline II helix


Prion protein


Rotational resonance


Rotational-echo double-resonance


Raman optical activity


Scanning electron microscopy


Surface-enhanced Raman spectroscopy


Solid-state nuclear magnetic resonance


Scanning transmission electron microscopy


Scanning tunneling microscopy


Transition dipole coupling


Transferred-echo double-resonance


Transmission electron microscopy


Tip-enhanced Raman spectroscopy




Vibrational circular dichroism


X-ray diffraction



The authors would like to acknowledge funding from the Natural Sciences and Engineering Research Council of Canada (NSERC), the Fonds de recherche du Québec - Nature et Technologies (FRQNT), the Regroupement québécois de recherche sur la fonction, l’ingénierie et les applications des protéines (PROTEO), the Centre de recherche sur les matériaux avancés (CERMA) and the Centre québécois sur les matériaux fonctionnels (CQMF). B.M. would like to acknowledge graduate scholarships from Bionano (NSERC) and PROTEO.

Compliance with ethical standards

Conflicts of interest

Benjamin Martial declares that he has no conflict of interest. Thierry Lefèvre declares that he has no conflict of interest. Michèle Auger declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemistry, Regroupement québécois de recherche sur la fonction, l’ingénierie et les applications des protéines (PROTEO), Centre de recherche sur les matériaux avancés (CERMA), Centre québécois sur les matériaux fonctionnels (CQMF)Université LavalQuébecCanada

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