Nanoscale Function Group, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland. khizar
Chem Phys Lipids. 2012 Feb;165(2):142-50. doi: 10.1016/j.chemphyslip.2011.11.011. Epub 2011 Dec 9.
Membrane interactions with β-amyloid peptides are implicated in the pathology of Alzheimer's disease and cholesterol has been shown to be key modulator of this interaction, yet little is known about the mechanism of this interaction. Using atomic force microscopy, we investigated the interaction of monomeric Aβ(1-40) peptides with planar mica-supported bilayers composed of DOPC and DPPC containing varying concentrations of cholesterol. We show that below the bilayer melting temperature, Aβ monomers adsorb to, and assemble on, the surface of DPPC bilayers to form layers that grow laterally and normal to the bilayer plane. Above the bilayer melting temperature, we observe protofibril formation. In contrast, in DOPC bilayers, Aβ monomers exhibit a detergent-like action, forming defects in the bilayer structure. The kinetics of both modes of interaction significantly increases with increasing membrane cholesterol content. We conclude that the mode and rate of the interaction of Aβ monomers with lipid bilayers are strongly dependent on lipid composition, phase state and cholesterol content.
β-淀粉样肽与膜的相互作用与阿尔茨海默病的病理学有关，胆固醇已被证明是这种相互作用的关键调节剂，但人们对这种相互作用的机制知之甚少。使用原子力显微镜，我们研究了单体 Aβ(1-40)肽与由 DOPC 和 DPPC 组成的平面云母支持双层膜的相互作用，其中包含不同浓度的胆固醇。我们表明，在双层膜熔点以下，Aβ 单体吸附在 DPPC 双层膜的表面上，并在其上组装，形成侧向和垂直于双层膜平面生长的层。在双层膜熔点以上，我们观察到原纤维的形成。相比之下，在 DOPC 双层膜中，Aβ 单体表现出去污剂样的作用，在双层膜结构中形成缺陷。两种相互作用模式的动力学都随着膜胆固醇含量的增加而显著增加。我们得出结论，Aβ 单体与脂质双层的相互作用模式和速率强烈依赖于脂质组成、相态和胆固醇含量。
