Abstract
The amyloid-beta peptide (Aβ) is considered a key factor in Alzheimer's disease (AD) ever since the discovery of the disease. The understanding of its damaging influence has however shifted recently from large fibrils observed in the inter-cellular environment to the small oligomers interacting with a cell membrane. We studied the effect of temperature on the latter interactions by evaluating the structural characteristics of zwitterionic phosphatidylcholine (PC) membranes with incorporated Aβ25–35 peptide. By means of small angle neutron scattering (SANS), we have observed for the first time a spontaneous reformation of extruded unilamellar vesicles (EULVs) to discoidal bicelle-like structures (BLSs) and small unilamellar vesicles (SULVs). These changes in the membrane self-organization happen during the thermodynamic phase transitions of lipids and only in the presence of the peptide. We interpret the dramatic changes in the membrane's overall shape with parallel changes in its thickness as the Aβ25–35 triggered membrane damage and a consequent reorganization of its structure. The suggested process is consistent with an action of separate peptides or small size peptide oligomers rather than the result of large Aβ fibrils.
Highlights
The amyloid-beta peptide (Aβ) is considered a key factor in Alzheimer’s disease (AD) ever since the discovery of the disease
The diluted suspension of extruded unilamellar vesicles (EULVs) was utilized as the best model for structural investigations by small angle neutron scattering (SANS) that offers the desired structural parameters
By virtue of the scattering experiment principles, the low-q region of presented data is influenced for the most part by a form factor of the overall unilamellar vesicles (ULVs), while the high-q region is influenced by a form factor of the bilayer, and its thickness in particular
Summary
The amyloid-beta peptide (Aβ) is considered a key factor in Alzheimer’s disease (AD) ever since the discovery of the disease. By means of small angle neutron scattering (SANS), we have observed for the first time a spontaneous reformation of extruded unilamellar vesicles (EULVs) to discoidal bicelle-like structures (BLSs) and small unilamellar vesicles (SULVs) These changes in the membrane selforganization happen during the thermodynamic phase transitions of lipids and only in the presence of the peptide. The transformation from the membrane monomeric peptide to an aggregated fibril outside the membrane, has yet to be understood It was shown that these peptides and their interactions with the membrane in particular, may play a major role in triggering the onset of AD3. AD stages where Aβ appears in its non-aggregated forms, where we scrutinize the peptide-membrane interactions instead of those between the peptides themselves The latter has been observed ample times and can be accelerated significantly when the temperature increases. This was proposed p reviously[14]
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