Several different proteins and peptides readily self-assemble into highly organized fibrillar clusters that are characterized by supramolecular β-sheet structures. Such protein aggregates, also known as amyloid-like fibrils, have received a significant attention over the past decades due to both their connection with neurodegenerative disorders (e.g. Alzheimer’s and Parkinson’s) and their potential of being employed as bionanomaterials, thanks to their remarkable strength and rigidity. The ambitions of combatting protein aggregation related diseases and of creating sophisticated materials, necessitate to thoroughly understand the process of amyloid fibril formation. It is commonly accepted that protein fibrillation undergoes a nucleated polymerization mechanism, consisting of a nucleation step followed by monomer addition events. Moreover, there is also an increasing evidence that fibril breakage plays a key role in reshaping the fibril length distribution, which may have crucial implications on biological functions and on biomaterial properties. In this frame, there is an increasing interest in unravelling the mechanisms of fibril fragmentation, which are still largely unknown.
The aim of the present work is to deepen the mechanism of amyloid fibril breakage as a function of temperature and agitation rate. We aim to clarify the dependence of the fibril breakage rate constant, both on the fibril length as well as on the fragmentation position along the fibril longitudinal axis. More specifically, we are interested in establishing a link between the environmental conditions and the three mainly accepted breakage mechanisms: central mechanism (i.e. fibrils preferentially break in their center), erosion mechanism (i.e. fibrils preferentially break at their ends), and random mechanism (i.e. fibrils break with the same likelihood at any position). To do so, we compare the predictions of a deterministic kinetic model with the time evolution of fibril distributions measured by AFM for three proteins (β-lactoglobulin, insulin, and β2-microglobulin) under various conditions of temperature and mechanical agitation, employing own and literature data.[2-4]
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 Nicoud L.; Lazzari S.; Barragán D.B.; M. Morbidelli, J. Phys. Chem. B 2015, in press