Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, Dubna, Moscow Region 141980, Russia; Institute of Physics, Kazan Federal University, Kremlevskaya 18, Kazan 420008, Russia.
Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Joliot-Curie 6, Dubna, Moscow Region 141980, Russia.
Biophys Chem. 2024 Oct;313:107292. doi: 10.1016/j.bpc.2024.107292. Epub 2024 Jul 11.
We have studied the effect of calcium ions (Ca) at various concentrations on the structure of lipid vesicles in the presence of amyloid-beta peptide Aβ(25-35). In particular, we have investigated the influence of calcium ions on the formation of recently documented bicelle-like structures (BLSs) emerged as a result of Aβ(25-35) triggered membrane disintegration. First, we have shown by using small-angle X-ray and neutron scattering that peptide molecules rigidify the lipid bilayer of gel phase DPPC unilamellar vesicles (ULVs), while addition of the calcium ions to the system hinders this effect of Aβ(25-35). Secondly, the Aβ(25-35) demonstrates a critical peptide concentration at which the BLSs reorganize from ULVs due to heating and cooling the samples through the lipid main phase transition temperature (T). However, addition of calcium ions does not affect noticeably the Aβ-induced formation of BLSs and their structural parameters, though the changes in peptide's secondary structure, e.g. the increased α-helix fraction, has been registered by circular dichroism spectroscopy. Finally, according to P nuclear magnetic resonance (NMR) measurements, calcium ions do not affect the lipid-peptide arrangement in BLSs and their ability to align in the magnetic field of NMR spectrometer. The influences of various concentrations of calcium ions on the lipid-peptide interactions may prove biologically important because their local concentrations vary widely in in-vivo conditions. In the present work, calcium ions were investigated as a possible tool aimed at regulating the lipid-peptide interactions that demonstrated the disruptive effect of Aβ(25-35) on lipid membranes.
我们研究了不同浓度钙离子（Ca）对存在淀粉样β肽 Aβ（25-35）时脂质囊泡结构的影响。特别是，我们研究了钙离子对最近报道的双嗜性夹层样结构（BLS）形成的影响，这些结构是由于 Aβ（25-35）触发的膜破裂而出现的。首先，我们通过使用小角度 X 射线和中子散射表明，肽分子使凝胶相 DPPC 单层囊泡（ULV）的脂质双层变硬，而向体系中添加钙离子会阻碍 Aβ（25-35）的这种作用。其次，Aβ（25-35）在临界肽浓度下表现出由于加热和冷却样品通过脂质主相变温度（T），BLS 从 ULV 重新组织。然而，添加钙离子不会明显影响 Aβ 诱导的 BLS 形成及其结构参数，尽管圆二色性光谱已记录到肽二级结构的变化，例如α-螺旋分数增加。最后，根据 P 核磁共振（NMR）测量，钙离子不会影响 BLS 中的脂质-肽排列及其在 NMR 光谱仪磁场中排列的能力。各种浓度的钙离子对脂质-肽相互作用的影响可能具有生物学意义，因为它们在体内条件下的局部浓度差异很大。在本工作中，钙离子被研究为一种可能的工具，旨在调节脂质-肽相互作用，这些相互作用表现出 Aβ（25-35）对脂质膜的破坏作用。
