Comparative analysis of the relative fragmentation stabilities of polymorphic amyloid fibrils

Wei-Feng Xue (U of Kent)

Nov 24. 2022, 16:00 — 16:45

The division of amyloid fibril particles through fragmentation is implicated in the progression of human neurodegenerative disorders such as Alzheimer's and Parkinson’s diseases. Fragmentation of amyloid fibrils plays a crucial role in the propagation of the amyloid state encoded in their three-dimensional structures and may have an important role in the spreading of potentially pathological properties and phenotypes in amyloid-associated diseases. However, despite the mechanistic importance of fibril fragmentation, the relative stabilities of different types or different polymorphs of amyloid fibrils toward fragmentation remains to be quantified. We have recently developed an analytical approach to compare the relative stabilities of different types of amyloid fibrils toward fragmentation, based on inversion formulae to recover the division rates information from time-dependent experimental measurements of filament size distributions. Here, applying our analytical approach, we show that controlled sonication, a widely used experimental method of mechanical perturbation for amyloid seed generation, can be used as a form of mechanical perturbation for rapid comparative assessment of the relative fragmentation stabilities of polymorphic amyloid fibril structures. Our conclusions show that fragmentation stabilities of different amyloid fibril polymorph structures can be diverse and suggest that the approach we report here will be useful in comparing the relative stabilities of amyloid fibril types or fibril polymorphs toward fragmentation under different biological conditions.

Further Information
ESI Boltzmann Lecture Hall
Associated Event:
Mathematical Methods for the Study of Self-organization in the Biological Sciences (Thematic Programme)
Pierre Degond (IMT)
Marie Doumic (Sorbonne U, Paris)
Anna Kicheva (ISTA, Klosterneuburg)
Sara Merino-Aceituno (U of Vienna)
Christian Schmeiser (U of Vienna)