Profile of changes in lipid bilayer structure caused by beta-amyloid peptide

beta -Amyloid peptide (A beta) is the primary constituent of senile plaques , a defining feature of Alzheimer's disease. Aggregated A beta is toxic to neurons, but the mechanism of toxicity is uncertain. One hypothesis is that interactions between A beta aggregates and cell membranes mediate A beta t oxicity. Previously, we described a positive correlation between the A beta aggregation state and surface hydrophobicity, and the ability of the pepti de to decrease fluidity in the center of the membrane bilayer [Kremer, J. J ., et al. (2000) Biochemistry 39, 10309-10318]. In this work, we report tha t A beta aggregates increased the steady-state anisotropy of 1,6-diphenyl-1 ,3,5-hexatriene (DPH) embedded in the hydrophobic center of the membrane in phospholipids with anionic, cationic, and zwitterionic headgroups, suggest ing that specific charge-charge interactions are not required for A beta -m embrane interactions. A beta did not affect the fluorescence lifetime of DP H, indicating that the increase in anisotropy is due to increased ordering of the phospholipid acyl chains rather than changes in water penetration in to the bilayer interior. A beta aggregates affected membrane fluidity above , but not below, the lipid phase-transition temperature and did not alter t he temperature or enthalpy of the phospholipid phase transition. A beta ind uced little to no change in membrane structure or water penetration near th e bilayer surface. Overall, these results suggest that exposed hydrophobic patches on the A beta aggregates interact with the hydrophobic core of the lipid bilayer, leading to a reduction in membrane fluidity. Decreases in me mbrane fluidity could hamper functioning of cell surface receptors and ion channel proteins; such decreases have been associated with cellular toxicit y.