Protein Misfolding & Amyloid Aggregation Kinetics

Nucleation-elongation mechanism underlying Alzheimer's, Parkinson's, and prion diseases

Total protein M₀ (μM)20 μM

Primary nucleation k_n10 ×10⁻⁶

Elongation k_e30 ×10⁻³

Secondary nucleation k_240 ×10⁻⁴

Critical nucleus n_cn_c = 2

Kinetic Parameters

Lag time t½—

Max rate—

Final conversion—

κ (rate const)—

Amyloid aggregation follows a nucleation-elongation mechanism (Knowles 2009, Science). Primary nucleation (rate ∝ m^n_c) creates initial seeds. Elongation (rate ∝ m·P) extends fibrils. Secondary nucleation (rate ∝ m²·P) on fibril surfaces is autocatalytic and produces the sigmoidal kinetics. Integrated rate law: M(t) ≈ M₀·[1 − e^(−(t/τ)²)] in the lag phase regime. The nucleation-free seeding protocol can bypass the lag phase entirely — a key experimental observation in prion biology.