Rapid Fragmentation during Seeded Lysozyme Aggregation Revealed at the Single Molecule Level.

Area of Science:

• Biochemistry
• Molecular Biology
• Neuroscience

Background:

• Protein aggregation, particularly amyloid formation, is implicated in neurodegenerative disorders like Alzheimer's and Parkinson's diseases.
• The precise pathogenic mechanisms of amyloid diseases remain poorly understood, hindering early diagnostics and therapeutic interventions.
• Seeded polymerization is a common model for studying amyloid formation, influencing lag phase duration and fibril growth.

Purpose of the Study:

• To elucidate the unclear mechanism of amyloid seeding.
• To investigate the role of seed fibrils in amyloid propagation.
• To understand the initial events in seeded polymerization.

Main Methods:

• Studying seeded polymerization dynamics.
• Observing seed fibril fragmentation (lateral and axial).
• Analyzing the generation of oligomers in the presence of monomers.

Main Results:

• Demonstrated lateral and axial fragmentation of seed fibrils.
• Observed the generation of oligomers from fragmented seeds.
• Showcased accelerated fibril growth following fragmentation and oligomerization.

Conclusions:

• Seed fibril fragmentation is a key early event in seeded polymerization.
• This fragmentation process contributes to the generation of new amyloid species.
• Understanding these mechanisms is critical for developing diagnostics and therapeutics for amyloid diseases.