Multimodal Spectroscopic Study of Amyloid Fibril Polymorphism

Area of Science:

• Biophysics
• Materials Science
• Protein Chemistry

Background:

• Amyloid fibrils are protein aggregates with a common beta-sheet core but variable surface structures.
• Polymorphism in amyloid fibrils leads to different morphologies and properties.
• Understanding surface structure is key to explaining fibril variations.

Purpose of the Study:

• To investigate structural differences between polymorphic amyloid fibrils using multimodal spectroscopy.
• To correlate surface molecular structure with fibril morphology and rigidity.
• To demonstrate the utility of surface-sensitive techniques in amyloid research.

Main Methods:

• Utilized a range of bulk- and surface-sensitive spectroscopic techniques.
• Employed mass spectrometry to analyze peptide composition.
• Applied tip-enhanced Raman spectroscopy (TERS) for nanometer-resolution surface analysis.
• Corroborated findings with vibrational sum-frequency generation (VSFG) spectroscopy.

Main Results:

• Mass spectrometry showed similar peptide composition for different fibril types.
• Bulk-sensitive spectroscopy revealed no structural differences between straight and wormlike fibrils.
• TERS demonstrated heterogeneous surface structures (unordered/alpha-helical) on both fibril types.
• Long, straight fibrils exhibited significantly more surface beta-sheet structure than short, wormlike fibrils.

Conclusions:

• Surface-specific advanced vibrational spectroscopy (TERS, VSFG) is crucial for distinguishing amyloid fibril polymorphs.
• Differences in surface beta-sheet content correlate with observed variations in fibril morphology and rigidity.
• These findings have implications for understanding diverse amyloid-related proteins in food and disease contexts.