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

R. Preston Mason, Robert F. Jacob, Mary F. Walter, Pamela E. Mason, Nicolai A. Avdulov, Svetlana V. Chochina, Urule Igbavboa, W. Gibson Wood

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)18801-18807
Number of pages7
JournalJournal of Biological Chemistry
Volume274
Issue number26
DOIs
StatePublished - Jun 25 1999

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