Epitaxial assembly dynamics of mutant amyloid β25-35_N27C fibrils explored with time-resolved scanning force microscopy.

Amyloid β25-35 (Aβ25-35) is a toxic fragment of Alzheimer's beta peptide. We have previously shown that Aβ25-35 fibrils form a trigonally oriented network on mica by epitaxial growth mechanisms. Chemical reactivity can be furnished to the fibril by introducing a cysteine residue (Aβ25-35_N27C) while maintaining oriented assembly properties. Previously we have shown that fibril binding to mica is strongly influenced by KCl concentration. In the present work we explored the kinetics of epitaxial assembly of the mutant fibrils at different peptide and KCl concentrations by using in situ time-resolved AFM. We measured the length of Aβ25-35_N27C fibrils as a function of time. Increasing free peptide concentration enhanced fibril growth rate, and the critical peptide concentration of fibril assembly was 3.92μM. Increasing KCl concentration decreased the number of fibrils bound to the mica surface, and above 20mM KCl fibril formation was completely abolished even at high peptide concentrations. By modulating peptide and KCl concentrations in the optimal ranges established here the complexity of the Aβ25-35_N27C network can be finely tuned.