ELUCIDATING AMYLIN PEPTIDE STRUCTURAL PROPERTIES BY EXPERIMENTAL TECHNIQUES AND MD SIMULATIONS

A wide range of proteomic studies shows that more than a third of proteins in eukaryotic organisms exhibit intrinsically disordered behaviour in specific regions or throughout their entire structure. These proteins can adopt various conformations, including a beta-sheet-like structure, and can stack on top of each other to form amyloid fibers. These amyloid fibers often gather in plaques in human tissue and are associated with various diseases. One example is the aggregation of the amylin peptide (or hIAPP) in pancreatic tissue, forming amyloid fibrils associated with type 2 diabetes mellitus (T2DM). hIAPP is a 37-residue peptide produced by beta cells in Langerhans islets, and its dysfunction is related to T2DM, but the causes, mechanisms of aggregation, and chemical pathways are not yet fully understood.

This work aims to elucidate the mechanisms of hIAPP fibrillation and characterize it in solution when interacting with lipid model membranes that mimic pancreatic beta cells. To this end, we aim to study this system through a combination of in vitro characterization experiments, such as small-angle X-ray scattering (SAXS), circular dichroism (CD) and optical microscopy, alongside an in silico approach involving molecular dynamics (MD) simulations of the system.