Tracking of nanoscale structural variations on a single amyloid fibril with tip-enhanced Raman scattering.

Amyloid fibrils are known to be responsible for diseases such as Alzheimer's disease. A detailed insight into the structure of amyloid fibrils is fundamental since it is not yet understood what triggers the misfolding of proteins to the fiber like structures. The molecular structure of fibril surfaces on a single amino acid level has not been revealed so far but would present a valuable contribution to this question. Here we demonstrate the direct molecular distinction of selected amino acids on insulin fibril surfaces with a lateral resolution better than 2 nm by applying tip-enhanced Raman spectroscopy (TERS). This approach provides simultaneously a way to directly reveal conformational changes in the secondary structure, namely α-helix, β-sheet, on the fibril surface with nanometer resolution.