Fragmentation of amyloid fibrils occurs in preferential positions depending on the environmental conditions.

Understanding the mechanism of amyloid fibril breakage is of fundamental importance in various research fields including biomedicine and bionanotechnology. The aim of this work is to clarify the impact of temperature and agitation speed on the fibril breakage rate constant, which depends both on the fibril length as well as on the position of fragmentation along the fibril longitudinal axis. In particular, we intend to discriminate between three fibril fragmentation mechanisms: erosion (i.e., breakage occurs preferentially at the ends of the fibril), random (i.e., breakage occurs with the same likelihood at any position), or central (i.e., breakage occurs preferentially at the center of the fibril). To do so, we compare the time evolution of the fibril length distribution followed with atomic force microscopy with simulations from a kinetic model based on population balance equations (PBE). In this frame, we investigate the breakage mechanism of insulin fibrils, which turns out to be affected by the operative conditions employed. Moreover, we compare our findings with literature data obtained with β-lactoglobulin and β2-microglobulin. It is observed that high temperature drives the breakage toward an erosion mechanism, while a high agitation rate rather induces a central breakage.