Non-electrostatic binding and self-association of amyloid beta-peptide on the surface of tightly packed phosphatidylcholine membranes.

Self-association of amyloid beta-peptide (Abeta) is considered to be an initial step in the development of Alzheimer's disease and is known to be promoted by negatively charged lipid membranes. We have examined the possibility of non-electrostatic Abeta-membrane interaction by using neutral phosphatidylcholine lipids. Fluorescence and circular dichroism spectra have clearly shown that Abeta binds to the phosphatidylcholine membrane in the lamellar gel phase but not in the ripple gel or liquid crystalline phase, indicating the importance of the tight lipid packing characteristic of the lamellar gel phase. The Abeta-membrane binding occurs at both low and high salt concentrations, ensuring the non-electrostatic nature of the interaction. The membrane-bound Abeta molecule takes a monomeric alpha-helical or self-associated beta-sheet structure depending on the temperature, peptide/lipid ratio, and salt concentration. The flat surface of tightly packed phosphatidylcholine membranes appears to serve as a platform for non-electrostatic binding and self-association of Abeta.