Total Internal Reflection Tip-Enhanced Raman Spectroscopy of Tau Fibrils

J Phys Chem B. 2022 Jul 14;126(27):5024-5032. doi: 10.1021/acs.jpcb.2c02786. Epub 2022 Jun 29.

Abstract

Total internal reflection tip-enhanced Raman spectroscopy (TIR-TERS) has recently emerged as a promising technique for noninvasive nanoscale chemical characterization of biomolecules. We demonstrate that the TERS enhancement achieved in this experimental configuration is nearly 30 times higher than that in linear polarization and 8 times higher than that in radial polarization using traditional bottom-illumination geometry. TIR-TERS is applied to the study of Tau amyloid fibrils formed with the human full-length Tau protein mixed with heparin. This technique reveals the possibility to perform TERS imaging with 1-4 nm axial and 5-10 nm lateral spatial optical resolution. In these Tau/heparin fibrils, spectral signatures assigned to aromatic amino acid residues (phenylalanine, histidine, and tyrosine) and nonaromatic ones (e.g., cysteine, lysine, arginine, asparagine, and glutamine) are distinctly observed. Amide I and amide III bands can also be detected. In a fibril portion, it is shown that antiparallel β-sheets and fibril core β-sheets are abundant and are often localized in amino acid-rich regions where parallel β-sheets and random coils are present in lower proportions. This first TIR-TERS study on a nonresonant biological sample paves the way for future nanoscale chemical and structural characterization of biomolecules using this performant and original technique.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides
  • Amyloid / chemistry
  • Heparin
  • Humans
  • Spectrum Analysis, Raman* / methods
  • tau Proteins*

Substances

  • Amides
  • Amyloid
  • tau Proteins
  • Heparin