The route to protein aggregate superstructures: Particulates and amyloid-like spherulites

Depending on external conditions, native proteins may change their structure and undergo different association routes leading to a large scale polymorphism of the aggregates. This feature has been widely observed but is not fully understood yet. This review focuses on morphologies, physico-chemical properties and mechanisms of formation of amyloid structures and protein superstructures. In particular, the main focus will be on protein particulates and amyloid-like spherulites, briefly summarizing possible experimental methods of analysis. Moreover, we will highlight the role of protein conformational changes and dominant forces in driving association together with their connection with the final aggregate structure. Eventually, we will discuss future perspectives in this field and we will comment what is, in our opinion, urgently needed.