Figure 2. Nucleation-dependent polymerization model of amyloid aggregation.

Amyloid formation consists of two phases: (i) a nucleation phase/lag phase, in which monomers undergo conformational change/misfolding and associate to form oligomeric nuclei, and (ii) a elongation phase/growth phase, in which the nuclei rapidly grow by further addition of monomers and form larger polymers/fibrils until saturation. The ‘nucleation phase‘, is thermodynamically unfavourable and occurs gradually, whereas ‘elongation phase’, is much more favourable process and proceeds quickly. Thus, kinetics of amyloid formation is well represented by a sigmoidal curve with a lag phase followed by rapid growth phase (green curve). The rate limiting step in the process is the formation of nuclei/seeds to promote aggregation. Thus, amyloid formation can be substantially speedup by the addition of preformed seeds (nuclei). The addition of seeds reduces the lag time and induces faster aggregate formation (red curve).