Self-Coiling of Single-Stranded Protofibrils into Rings: A Pathway of Alzheimer's β-Peptide Amyloidosis on Lipid...

An amyloidosis pathway of Alzheimer's β-peptide Aβ40 on lipid membranes, the self-coiling of single-stranded protofibrils into thermodynamically stable ring structures, is uncovered. Distinct from Aβ amyloid structures reported previously, the coiled rings observed here exhibit a narrow distribution of diameters centered at ∼170 nm and their circumference thicknesses increase as a longer single-stranded protofibril wraps around the ring, indicating the coaxial loop-by-loop winding of individual protofibrils. Such self-coiling is dominated by elastic properties of the flexible protofibrils subject to thermal fluctuations and surface interactions, as supported by an entropic elasticity model from polymer physics concepts. This work not only provides insights into the fundamental physics of Alzheimer's β-peptide amyloidosis but also is useful for designing amyloid filament materials.