Characterization of Amyloid Fibril Bundling in Hen Egg White Lysozyme

Amyloids are proteins that, in their misfolded conformations, self-assemble into non-branching rigid fibrils. Growth of these fibrils involves both primary and secondary nucleation processes, resulting in “sigmoidal” growth kinetics. These fibrils can further bundle together and form large sheets known as amyloid plaques. Although these plaques are no longer believed to be the primary pathogenic aggregate in neurodegenerative diseases such as Alzheimer's Disease, they are prominent contributors to non-neuropathic anyloidoses. In cardiac amyloidosis plaques restrict contraction of the ventricles, leading to arrythmia and heart failure. However the mechanisms driving assembly of plaques from individual fibrils have remained elusive. 

This study combined optical microscopy, transmission electron microscopy, and Thioflavin T fluorescence assays to determine if amyloid fibril bundling in hen egg white lysozyme  resulted from equilibrium association of RFs or from fibril-mediated secondary nucleation during growth. The data gathered suggests that amyloid plaques can form independent of fibril growth, with RF length not significantly impacting plaque formation. However, the degree of plaque formation is significantly enhanced during growth, most likely due to secondary nucleation.