Schematic panels describing AFBs hypothetical behavior in detecting different αS species in the cellular environment. (A) Intra-AFB could, theoretically, sense the native state of αS (globular monomeric or the bidirectional conversion to a membrane-bound multimeric, as shown by the double arrows) as well as aggregated forms. In our system, though, Intra-AFB is sensitive only to the native state of αS, since when aggregation is stimulated no significant variation of FRET signal for the intra-AFB is recorded (crossed arrow). (B) Inter-AFB can sense only HMW species under pro-aggregating conditions, at a distance of 2–10 nm, according to FRET principles, but cannot detect native multimeric αS structures bound to membranes as described by Burrè et al. [38], probably because the fluorophores are too distant.