Distribution and fluidizing action of soluble and aggregated amyloid β- peptide in rat synaptic plasma membranes

Abstract

The effects of soluble and aggregated amyloid β-peptide (Aβ) on cortical synaptic plasma membrane (SPM) structure were examined using small angle x-ray diffraction and fluorescence spectroscopy approaches. Electron density profiles generated from the x-ray diffraction data demonstrated that soluble and aggregated Aβ1-40 peptides associated with distinct regions of the SPM. The width of the SPM samples, including surface hydration, was 84 Å at 10 °C. Following addition of soluble Aβ1-40, there was a broad increase in electron density in the SPM hydrocarbon core ±0-15 Å from the membrane center, and a reduction in hydrocarbon core width by 6 Å. By contrast, aggregated Aβ1-40 contributed electron density to the phospholipid headgroup/hydrated surface of the SPM ±24-37 Å from the membrane center, concomitant with an increase in molecular volume in the hydrocarbon core. The SPM interactions observed for Aβ1-40 were reproduced in a brain lipid membrane system. In contrast to A2b1-40, aggregated Aβ1-42 intercalated into the lipid bilayer hydrocarbon core ±0-12 Å from the membrane center. Fluorescence experiments showed that both soluble and aggregated Aβ1-40 significantly increased SPM bulk and protein annular fluidity. Physico-chemical interactions of Aβ with the neuronal membrane may contribute to mechanisms of neurotoxicity, independent of specific receptor binding.