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

The effects of soluble and aggregated amyloid P-peptide (AP) on cortical sy naptic plasma membrane (SPM) structure were examined using small angle x-ra y diffraction and fluorescence spectroscopy approaches, Electron density pr ofiles generated from the x-ray diffraction data demonstrated that soluble and aggregated A beta(1-40) peptides associated with distinct regions of th e SPM, The width of the SPM samples, including surface hydration, was 84 An gstrom at 10 degrees C, Following addition of soluble A beta(1-40), there w as a broad increase in electron density in the SPM hydrocarbon core +/-0-15 Angstrom from the membrane center, and a reduction in hydrocarbon core wid th by 6 Angstrom. By contrast, aggregated A beta(1-40) contributed electron density to the phospholipid headgroup/hydrated surface of the SPM +/-24-37 Angstrom from the membrane center, concomitant with an increase in molecul ar volume in the hydrocarbon core, The SPM interactions observed for A beta (1-40) were reproduced in a brain lipid membrane system, In contrast to A b eta(1-40), aggregated A beta(1-42) intercalated into the lipid bilayer hydr ocarbon core +/-0-12 Angstrom from the membrane center. Fluorescence experi ments showed that both soluble and aggregated A beta(1-40) significantly in creased SPM bulk and protein annular fluidity, Physico chemical interaction s of AP with the neuronal membrane may contribute to mechanisms of neurotox icity, independent of specific receptor binding.