Amyloid formation follows a sigmoidal kinetic curve with a lag phase (slow nucleation), exponential growth phase (fibril elongation), and saturation. The critical nucleus is typically 2-6 monomers. Once fibrils form, they fragment and each fragment is a new seed — secondary nucleation dramatically accelerates aggregation (Knowles et al., 2009).
Misfolded proteins can template conformational change in native proteins through direct physical contact. α-synuclein (Parkinson's), tau (Alzheimer's), and TDP-43 (ALS) all show prion-like spreading between cells. The cell-to-cell transmission follows neural connectivity — staging matches Braak staging in human post-mortem tissue.
Hsp70, Hsp90, and the chaperonin GroEL/ES recognize exposed hydrophobic patches on misfolded proteins and attempt to refold them (at ATP cost). When the unfolded protein response is overwhelmed, the ubiquitin-proteasome system marks proteins for degradation. Therapeutic strategies target disaggregases (Hsp104) to dissolve existing fibrils.