The surface activity of Alzheimer's disease amyloid-β peptide (Aβ) may play a key role in its structural and aggregation dynamics. The Aβ peptide is amphiphilic, with a hydrophilic and charged N-terminal region and a hydrophobic C-terminal region that belongs to the transmembrane domain of the amyloid precursor protein. Experimentally, Aβ40 readily adsorbs to the air-water interface, where a surface pressure of 14mN/m is reached from a low Aβ bulk concentration of 250nM. We show here that the air-water interface can modulate the conformation and ordering of the Aβ peptide and templating the assembly of Aβ into fibrils.

To gain structural information on the Aβ peptide adsorbed at the air-water interface, we carried out grazing incident X-ray diffraction (GIXD) and X-ray reflectivity (XR) experiments. We found that Aβ adsorbed to the air-water interface from a pure water subphase (pH ~ 5.5) where the peptide is largely a random coil, showed lateral crystalline ordering that corresponds to β-sheet spacing when the peptide assembles into fibrils. The air-water interface thus induced structural transitions in Aβ that mimics those found in fibrils. Increasing the ionic strength of the subphase deceased the amount of ordering while increasing the pH to 7.2 abolished the ordering of the peptide at the air-water interface. To evaluate the effect of the air-water interface on Aβ fibril formation, Aβ with and without gentle rotation was incubated in different pH and ionic strength buffers. Aβ incubated at pH 5.5 formed amorphous precipitates during incubation while Aβ incubated at pH 7.2 formed mature fibrils. With rotation, Aβ incubated at pH 5.5 formed fibril-like aggregates. The ordered Aβ at the air-water interface thus induced the formation of structured aggregates.