Structure of Amyloid Peptide Ribbons Characterized by Electron Microscopy, Atomic Force Microscopy, and Solid-State...

Area of Science:

• Biochemistry
• Structural Biology
• Neuroscience

Background:

• Polypeptides self-assemble into amyloid fibrils with cross-β structures.
• Amyloid fragments can form ribbon-like assemblies with distinct morphologies.
• Alzheimer's disease-associated amyloid-beta peptide (Aβ) is implicated in fibril formation.

Purpose of the Study:

• To investigate the detailed structure of amyloid ribbons formed by Aβ_14-23 and Aβ_11-25.
• To elucidate the relationship between molecular structure and ribbon morphology.

Main Methods:

• Solid-state nuclear magnetic resonance (ssNMR) for β-sheet registry and hydrogen bonding.
• Dark-field transmission electron microscopy (TEM) for mass-per-area determination.
• Atomic force microscopy (AFM) for ribbon thickness measurement.
• Cryogenic electron microscopy (cryoEM) for β-sheet spacing analysis.

Main Results:

• ssNMR data revealed antiparallel β-sheets with specific intermolecular hydrogen bond registries.
• AFM confirmed a consistent ribbon thickness of approximately 5 nm.
• CryoEM showed periodic spacing of β-sheets within Aβ_14-23 ribbons.
• Mass-per-area values were derived from TEM data.

Conclusions:

• Amyloid ribbon growth occurs along the direction of intermolecular hydrogen bonds between β-strands.
• Ribbon thickness corresponds to the width of a single β-sheet.
• Variable ribbon width results from multiples of the β-sheet stacking repeat distance.
• This cross-β architecture may be common in amyloid ribbons.