Distribution and fluidizing action of soluble and aggregated amyloid beta-peptide in rat synaptic plasma membranes.
The effects of soluble and aggregated amyloid beta-peptide (Abeta) 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 Abeta1-40 peptides associated with distinct regions of the SPM. The width of the SPM samples, including surface hydration, was 84 A at 10 degrees C. Following addition of soluble Abeta1-40, there was a broad increase in electron density in the SPM hydrocarbon core +/-0-15 A from the membrane center, and a reduction in hydrocarbon core width by 6 A. By contrast, aggregated Abeta1-40 contributed electron density to the phospholipid headgroup/hydrated surface of the SPM +/-24-37 A from the membrane center, concomitant with an increase in molecular volume in the hydrocarbon core. The SPM interactions observed for Abeta1-40 were reproduced in a brain lipid membrane system. In contrast to Abeta1-40, aggregated Abeta1-42 intercalated into the lipid bilayer hydrocarbon core +/-0-12 A from the membrane center. Fluorescence experiments showed that both soluble and aggregated Abeta1-40 significantly increased SPM bulk and protein annular fluidity. Physico-chemical interactions of Abeta with the neuronal membrane may contribute to mechanisms of neurotoxicity, independent of specific receptor binding.
Mason
R P
RP
Membrane Biophysics Laboratory, Departments of Medicine and Biochemistry, MCP Hahnemann University School of Medicine, Allegheny Campus, Pittsburgh, Pennsylvania 15212-4772, USA.
Jacob
R F
RF
Walter
M F
MF
Mason
P E
PE
Avdulov
N A
NA
Chochina
S V
SV
Igbavboa
U
U
Wood
W G
WG
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D008297:Male; D008958:Models, Molecular; D011487:Protein Conformation; D051381:Rats; D011916:Rats, Inbred F344; D012995:Solubility; D013570:Synaptic Membranes / Q000378:metabolism*
D016229:Amyloid beta-Peptides