Amyloid-β peptides time-dependent structural modifications: AFM and voltammetric characterization.

Area of Science:

• Biochemistry
• Biophysics
• Materials Science

Background:

• Amyloid beta (Aβ) peptides, particularly Aβ1-40 and Aβ1-42, are implicated in neurodegenerative diseases.
• Understanding the structural modifications of Aβ peptides from monomers to fibrils is crucial for disease research.

Purpose of the Study:

• To investigate the structural modifications of human Aβ peptides (Aβ1-40, Aβ1-42) and compare them with various modified and non-human sequences.
• To elucidate the sequence-structure relationship governing Aβ peptide aggregation pathways and kinetics.
• To explore the influence of carbon electrode surfaces on Aβ peptide conformation and fibril morphology.

Main Methods:

• Atomic Force Microscopy (AFM) to visualize structural changes from monomers to fibrils.
• Electrochemical techniques, including Differential Pulse Voltammetry, to monitor peptide oxidation and detect fibrillization.
• Controlled aggregation experiments in chloride-free media at room temperature.

Main Results:

• Aβ aggregation is a sequence-structure dependent process occurring at different rates and pathways.
• AFM revealed distinct morphological transitions from random coils to aggregates, protofibrils, and β-sheet rich fibrils.
• Hydrophobic carbon surfaces induced rapid conformational changes and distinct fibril morphologies compared to solution.
• Electrochemical detection showed Aβ peptides undergo oxidation in one or two steps, with fibrillization correlating to decreased oxidation peak currents.

Conclusions:

• The primary sequence and physicochemical properties dictate Aβ peptide aggregation pathways and kinetics.
• Aβ fibril formation can be monitored and characterized using a combination of AFM and electrochemical methods.
• Surface properties significantly influence Aβ peptide conformation and fibril characteristics, offering insights into potential therapeutic strategies.