Identification of the Fragmentation Role in the Amyloid Assembling Processes and Application to their Optimization

Abstract

The goal is to establish a kinetic model of amyloid formation which will take into account the contribution of fragmentation to the de novo creation of templating interfaces. We propose a new, more comprehensive mathematical model which takes into account previously neglected phenomena potentially occurring during the templating and fragmentation processes. In particular, we try to capture a potential effect of the topology and geometry of prion folding on the elongation and fragmentation properties of a polymer of a given length by separating polymers of the same length into several compartments. Additionally, we apply techniques from geometric control to the new model to design optimal strategies for accelerating the current amplification protocols, such as the Protein Misfolding Cyclic Amplification (PMCA). The objective is to reduce the time needed to diagnose many neurodegenerative diseases. Determining the optimal strategy for accelerated replication in the general problem of fragmentation optimization is still an open question.