The structural and mechanical characterization of biological systems and interfaces for the study of protein misfolding diseases

My PhD project involved the use of high-resolution microscopy techniques to study the mechanisms driving neurodegeneration in protein aggregation diseases, and to investigate the effects of anti-aggregation drugs. Several pieces of evidence indicate that in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, toxic behaviour could result from the action of amyloid aggregates. The latter are highly organized and insoluble aggregates that are formed upon misfolding and aggregation of soluble proteins which undergo destabilization of their native structure. These proteins share the common characteristic of aggregating into fibrillar structures, referred to as "amyloid fibrils" with a high content of β-sheets and specific cross-beta arrangement. The study was conducted using advanced atomic force microscopy (AFM) both as a single technique to mechanistically and structurally characterize biological systems and interfaces involved in the interaction with toxic protein aggregates (through imaging and analysis of force/distance curves), and as a combined technique, together with optical microscopy, to understand the molecular mechanisms of protein aggregation, which represents a crucial problem to counteract misfolded protein diseases.