Visualizing Super-Diffusion, Oligomerization, and Fibrillation of Amyloid-β Peptide Chains along Tubular Membranes.

A deeper mechanistic study of peptide amyloidosis on lipid membranes with varying shapes could enhance the comprehensive understanding of the contribution of cellular structures to multiple neurodegenerative diseases, including Alzheimer's disease. We report here the direct visual observation of amyloid-β peptide (Aβ) superdiffusing along tubular lipid membranes via single-molecule tracking (SMT). Such mobility on tubular membranes is critical, as it allows Aβ chains to oligomerize and elongate into fibrils. Factors such as cholesterol that favor Aβ chains with sufficient surface residence time can promote the inter-Aβ interaction and enhance Aβ fibrillation. This study provides previously uncharacterized insights into the chain behaviors of Aβ along important biological nanowire structures, which is essential to understanding and exploring the factors of cellular shapes to manipulate peptide amyloidosis.