Nanoscale Hyperspectral Imaging of Amyloid Secondary Structures in Liquid

Abstract

Abnormal aggregation of amyloid‐β is a very complex and heterogeneous process. Owing to methodological limitations, the aggregation pathway is still not fully understood. Herein a new approach is presented in which the secondary structure of single amyloid‐β aggregates is investigated with tip‐enhanced Raman spectroscopy (TERS) in a liquid environment. Clearly resolved TERS signatures of the amide I and amide III bands enabled a detailed analysis of the molecular structure of single aggregates at each phase of the primary aggregation of amyloid‐β and also of small species on the surface of fibrils attributed to secondary nucleation. Notably, a β‐sheet rearrangement from antiparallel in protofibrils to parallel in fibrils is observed. This study allows better understanding of Alzheimer's disease etiology and the methodology can be applied in studies of other neurodegenerative disorders.

Revealing DNA Structure at Liquid/Solid Interfaces by AFM-Based High-Resolution Imaging and Molecular Spectroscopy

“…Future developments in this field should be focused on searching methodological and technical solutions that allow to perform analogical experiments but under liquid conditions. The TERS findings obtained in liquid for amyloid-β showing the rearmament of secondary structure from protofibrils to fibrils conversion in the aggregation process, already proved the great potential of this technique applied in liquid environment in the research on structural transitions of biomolecules [107].…”

“…Measurements in liquids are especially beneficial for nanospectroscopic experiments Solvents prevent or largely prohibit damage and decomposition of samples, which may occur in strong, local electromagnetic field generated in TERS and SERS. The quality of spectral data precisely SNR is better for data acquired in liquid than in ambient conditions The protective role of liquids is complex and takes advantage from several temperature dependent physical phenomena and physical properties of solvents, plasmonic nanostructures, samples, and substrates [107].…”

“…The quality of spectral data precisely SNR is better for data acquired in liquid than in ambient conditions. The protective role of liquids is complex and takes advantage from several temperature dependent physical phenomena and physical properties of solvents, plasmonic nanostructures, samples, and substrates [107].…”

Challenges and Opportunities of Tip-Enhanced Raman Spectroscopy in Liquids

“…The liquid measurements enable a high SNR and reproducibility. 141 3.3.4. Modification of a STM Tip for Chemical Analysis.…”

“…139 Only few studies to date investigated biologically relevant samples, with examples being lipid bilayers 60 and amyloid-β peptide aggregates. 141 4.2. Challenges.…”