Surface effects on aggregation kinetics of amyloidogenic peptides

Area of Science:

• Biophysics
• Biochemistry
• Computational Biology

Background:

• Protein and peptide aggregation into fibrils is central to neurodegenerative diseases.
• Surface interactions significantly influence the kinetics of amyloid formation.
• Understanding these surface effects is crucial for developing therapeutic strategies.

Purpose of the Study:

• To systematically investigate the impact of surface properties on amyloidogenic peptide aggregation kinetics.
• To elucidate the molecular mechanisms governing surface-induced fibril formation.
• To correlate simulation findings with experimental observations in disease-relevant peptides.

Main Methods:

• Molecular dynamics simulations of model peptides interacting with surfaces.
• Thioflavin T fluorescence assays to monitor fibril formation kinetics.
• Experimental validation using alpha-synuclein and amyloid-beta peptides with controlled surface area (nanoparticles).

Main Results:

• Surface attraction non-linearly affects nucleation and oligomer growth: weak attraction retards, strong attraction accelerates.
• The effect of an attractive surface depends on the peptide's intrinsic fibril-forming propensity.
• Surface effects are governed by relative peptide-surface vs. peptide-bulk association and surface area to concentration ratio.

Conclusions:

• Surface interactions play a complex, context-dependent role in amyloid formation.
• Findings provide molecular insights into fibrillation in complex biological environments.
• This knowledge can guide the tuning of fibrillation in various systems, potentially impacting disease treatment.