Anionic lipids modulate little the reorganization effect of amyloid-beta peptides on membranes.

Amyloid-ß peptide interactions with model lipid membranes have been studied by means of small angle neutron scattering and molecular dynamics simulations. These interactions had been indicated recently as an origin of the membrane structure reorganizations between spherical small unilamellar vesicles and planar bicelle-like structures. In present work, we investigate the influence of charge on the peptide-triggered morphological changes by introducing the anionic lipid DMPS to the underlying DMPC membrane. Changes to the membrane thickness and the overall membrane structure with and without Aß25-35 incorporated have been investigated over a wide range of temperatures. Our results document the previously reported morphological reformations between bicelle-like structures present in gel phase and small unilamellar vesicles present in fluid phase to be independent from the charge existence in the system.

Amyloid-beta peptide (25-35) triggers a reorganization of lipid membranes driven by temperature changes.

The amyloid-beta peptide (Aß) 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 Aß25-35 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 Aß25-35 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 Aß fibrils.