Peptide aggregation in finite systems.

Universal features of the peptide aggregation process suggest a common mechanism, with a first-order phase transition in aqueous solutions of the peptides being the driving force. Small system sizes strongly affect the stability of the minor phase in the two-phase region. We show manifestations of this effect in aqueous solutions of fragments of the islet amyloid polypeptide, using computer simulation methods and invoking various approaches in characterizing clustering and aggregate formation. These systems with peptide concentrations deeply inside the immiscibility region show two distinct stable states, which interchange with time: one state contains a peptide aggregate; and the other state has an aggregate that is noticeably dissolved. The first state is relevant for macroscopic systems, whereas the second one is artificial. At a fixed concentration, the occurrence probability of the aggregate state vanishes upon decreasing the system size, thus indicating the necessity to apply a finite size-scaling for meaningful studies of peptide aggregation by simulations. The effect observed may be one of the factors responsible for the difference between intracellular and extracellular aggregation and fibrillization of polypeptides. The finite size of biological cells or their compartments may be playing a decisive role in hampering intracellular aggregation of highly insoluble amyloidogenic proteins, whereas aggregation is unavoidable in the extracellular space at the same peptide concentration.