Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, 141980, Dubna, Russia.
Institute for Safety Problems of Nuclear Power Plants, NAS of Ukraine, 03028, Kyiv, Ukraine.
Sci Rep. 2021 Nov 9;11(1):21990. doi: 10.1038/s41598-021-01347-7.
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 Aβ 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 Aβ 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.
淀粉样β肽（Aβ）被认为是阿尔茨海默病（AD）的关键因素，自从发现这种疾病以来一直如此。然而，最近对其有害影响的理解已经从细胞间环境中观察到的大纤维转变为与细胞膜相互作用的小寡聚体。我们通过评估含有 Aβ肽的离子型磷脂酰胆碱（PC）膜的结构特性来研究温度对后者相互作用的影响。通过小角中子散射（SANS），我们首次观察到挤出的单层囊泡（EULV）自发地重新形成盘状双脂体样结构（BLS）和小单层囊泡（SULV）。这种膜自组织的变化发生在脂质的热力学相变过程中，而且只有在肽的存在下才会发生。我们将膜整体形状的剧烈变化与厚度的平行变化解释为 Aβ触发的膜损伤和结构的相应重组。所提出的过程与单独的肽或小尺寸的肽寡聚体的作用一致，而不是大 Aβ纤维的结果。
