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Mica Lattice Orientation of Epitaxially Grown Amyloid β25-35 Fibrils
György G Ferenczy1, Ünige Murvai1, Lívia Fülöp2
1Department of Biophysics and Radiation Biology, Semmelweis University, Tűzoltó u. 37-47, 1094 Budapest, Hungary.
Abstract:
β-amyloid (Aβ) peptides form self-organizing fibrils in Alzheimer's disease. The biologically active, toxic Aβ25-35 fragment of the full-length Aβ-peptide forms a stable, oriented filament network on the mica surface with an epitaxial mechanism at the timescale of seconds. While many of the structural and dynamic features of the oriented Aβ25-35 fibrils have been investigated before, the β-strand arrangement of the fibrils and their exact orientation with respect to the mica lattice remained unknown. By using high-resolution atomic force microscopy, here, we show that the Aβ25-35 fibrils are oriented along the long diagonal of the oxygen hexagon of mica. To test the structure and stability of the oriented fibrils further, we carried out molecular dynamics simulations on model β-sheets. The models included the mica surface and a single fibril motif built from β-strands. We show that a sheet with parallel β-strands binds to the mica surface with its positively charged groups, but the C-terminals of the strands orient upward. In contrast, the model with antiparallel strands preserves its parallel orientation with the surface in the molecular dynamics simulation, suggesting that this model describes the first β-sheet layer of the mica-bound Aβ25-35 fibrils well. These results pave the way toward nanotechnological construction and applications for the designed amyloid peptides.
Insights
Alzheimer's disease amyloid-beta 25-35 fibrils form oriented networks on mica surfaces. Antiparallel beta-strand arrangements are key to their stable, surface-bound structure, offering insights for nanotech applications.
Area of Science:
- Biophysics
- Materials Science
- Neuroscience
Background:
- Alzheimer's disease is linked to beta-amyloid (Aβ) peptide fibril formation.
- The Aβ25-35 fragment self-organizes into stable, oriented filament networks on mica surfaces.
- Previous studies lacked detail on the β-strand arrangement and orientation of Aβ25-35 fibrils on mica.
Purpose of the Study:
- To determine the precise β-strand arrangement and orientation of Aβ25-35 fibrils on mica.
- To investigate the structural stability of these fibrils using molecular dynamics simulations.
- To explore potential nanotechnological applications based on designed amyloid peptides.
Main Methods:
- High-resolution atomic force microscopy (AFM) to visualize fibril structure and orientation.
- Molecular dynamics (MD) simulations of model β-sheets on a mica surface.
- Analysis of fibril orientation relative to the mica lattice structure.
Main Results:
- Aβ25-35 fibrils exhibit an epitaxial growth mechanism on mica.
- Fibrils are oriented along the long diagonal of the mica's oxygen hexagon.
- MD simulations suggest antiparallel β-strand arrangements are crucial for stable binding to the mica surface.
Conclusions:
- The study elucidates the specific orientation and β-strand configuration of Aβ25-35 fibrils on mica.
- Antiparallel β-sheet models accurately represent the interface between fibrils and the mica surface.
- Findings provide a foundation for developing novel nanotechnological constructs using amyloid peptides.
