Nanoscale structural and mechanical effects of beta-amyloid (1-42) on polymer cushioned membranes: A combined study by neutron reflectometry and AFM Force Spectroscopy
Nanoscale structural and mechanical effects of beta-amyloid (1-42) on polymer cushioned membranes: A combined study by neutron reflectometry and AFM Force Spectroscopy
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DOI：
10.1016/j.bbamem.2011.07.024
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发表时间：
2011-11-01
影响因子：
3.4
通讯作者：
Dencher, Norbert A.
中科院分区：
文献类型：
--
作者：
Dante, Silvia;Hauss, Thomas;Dencher, Norbert A.
β-淀粉样多肽与脂膜的相互作用被广泛研究为阿尔茨海默病的触发剂。它们在分子水平上的作用机制尚不清楚，它们与神经膜的相互作用对于阐明疾病的发生至关重要。在这项研究中，我们研究了水溶性形式的β-淀粉样蛋白Aβ(1-42)与聚合物垫支撑的脂双层之间的相互作用。用中子反射率改进了在生理条件下(PBS缓冲液，pH=7.4)制备模拟神经膜成分的支撑型磷脂膜的方法。用中子反射率和原子力显微镜(AFM)力谱研究了Aβ(1-42)存在时膜的结构和局部力学性能的变化。中子反射率表明，Aβ(1-42)与支撑膜发生强烈的相互作用，导致脂双层的散射长度密度分布发生变化，并穿透到膜中。同时，AFM力谱显示，通过与多肽的相互作用，双层的局部力学性能发生了很大的变化。这些结果可能对阿尔茨海默病的发病非常重要，因为脂质基质的结构和机械性质的同时变化可能会影响所有基于膜的信号级联。(C)2011爱思唯尔B.V.保留所有权利。
The interaction of beta-amyloid peptides with lipid membranes is widely studied as trigger agents in Alzheimer's disease. Their mechanism of action at the molecular level is unknown and their interaction with the neural membrane is crucial to elucidate the onset of the disease. In this study we have investigated the interaction of water soluble forms of beta-amyloid A beta(1-42) with lipid bilayers supported by polymer cushion. A reproducible protocol for the preparation of a supported phospholipid membrane with composition mimicking the neural membrane and in physiological condition (PBS buffer, pH = 7.4) was refined by neutron reflectivity. The change in structure and local mechanical properties of the membrane in the presence of A beta(1-42) was investigated by neutron reflectivity and Atomic Force Microscopy (AFM) Force Spectroscopy. Neutron reflectivity evidenced that A beta(1-42) interacts strongly with the supported membrane, causing a change in the scattering length density profile of the lipid bilayer, and penetrates into the membrane. Concomitantly, the local mechanical properties of the bilayer are deeply modified by the interaction with the peptide as seen by AFM Force Spectroscopy. These results may be of great importance for the onset of the Alzheimer's disease, since a simultaneous change in the structural and mechanical properties of the lipid matrix could influence all membrane based signal cascades. (C) 2011 Elsevier B.V. All rights reserved.