Mechanistic insights into peptide self-assembly, aggregation and amyloid inhibition

Guanghong Wei

Department of Physics, State Key Laboratory of Surface physics, Key Laboratory for Computational Physical Science (Ministry of Education), Fudan University, Shanghai 200433, China

Peptide self-assembly and amyloid aggregation have been received considerable attention due to their crucial roles in the design of nanomaterials and their links with a number of human diseases. For example, the self-assembled diphenylalanine (FF) nanotubes can be used as nanoscale molds for the casting of metallic nanowires, while the abnormal aggregation of amyloid-β peptide (Aβ) and human islet amyloid popypeptide (hIAPP) into amyloid fibrils is associated with respectively Alzheimers disease and type 2 diabetes. Due to the heterogeneous and transient nature of oligomers and the polymorphisms of fibrils, amyloid diseases are largely incurable and the mechanisms of peptide self-assembly/aggregation are not well understood. Here, I present our molecular dynamics simulation results of the self-assembly/aggregation of a few of peptides (including FF, Aβ fragments and hIAPP) and the inhibitory effects of small molecules/carbon nanoparticles on peptide aggregation. Atomic force microscopy and ThT experiments supporting our simulation results are also discussed. Our findings provide novel insights into microscopic mechanism of peptide self-assembly, aggregation and amyloid inhibition, which might be beneficial for the design of bio-nanostructures and the development of drug candidates against human amyloid diseases.