Exploring early stage processes involved in amyloid fibril formation

Amyloid fibrils are highly ordered polypeptide aggregates which form under a wide range of conditions. Their presence in vivo has been associated with a number of degenerative diseases, but is also utilised by several species in forming functional structures. Understanding and controlling the processes governing amyloid fibril formation can lead to prevention of these diseases as well as the possibility for constructing novel materials. Recently acquired high precision experimental data shows that several kinetic regimes for fibril growth exist at different protein concentration. I will present a series of simulation models with different early stage fibril formation mechanisms. These show that micelle formation by the protein can provide a concentration regime shift at the critical micelle concentration which resembles the experimental data. I also explore the later, growth stage and infer that a feedback mechanism such as fibril fragmentation is required to explain the experimental data.