Fig. 3: Controlling fibril growth defect frequency by varying supersaturation levels.

a Defects (purple) are initially formed by incorrect or incomplete binding of an incoming monomer onto the fibril end and subsequently kinetically trapped by attachment of further monomer layers on top of the misaligned monomer. Defects have been illustrated as lateral dislocations of the entire cross-section for convenience only: other defect structures are also possible. b at low enough monomer concentrations the rate of correct elongation and dissociation are close to equilibrium (the solubility limit). In this regime defect removal is faster than formation, and kinetic trapping is largely eliminated. c Aβ40 solubility decreases substantially with temperature from 64 to 37 °C ensuring elongation remains close to equilibrium at all times. Data are adapted from ref. ⁴⁹, except for the solubility at 60 °C, which we measured by NMR as shown in Supplementary Fig. 3. d We grow fibrils designed to be largely free of kinetically trapped growth defects, by slowly reducing the temperature of a solution of initially slightly supersaturated monomeric Aβ40 from 60 to 37 °C by 1 °C per hour. This ensures production of significant quantities of fibrils without requiring supersaturation.