Institute of Physical Chemistry , Polish Academy of Sciences , Kasprzaka 44/52 , 01-224 Warsaw , Poland.
Department of Chemistry , University of Guelph , 50 Stone Road East , Guelph , Ontario N1G 2W1 , Canada.
Langmuir. 2019 Sep 10;35(36):11940-11949. doi: 10.1021/acs.langmuir.9b01645. Epub 2019 Aug 5.
Amyloid β, Aβ(1-42), is a component of senile plaques present in the brain of Alzheimer's disease patients and one of the main suspects responsible for pathological consequences of the disease. Herein, we directly visualize the Aβ activity toward a brain-like model membrane and demonstrate that this activity strongly depends on the Aβ oligomer size. PeakForce quantitative nanomechanical mapping mode of atomic force microscopy imaging revealed that the interaction of large-size (LS) Aβ oligomers, corresponding to high-molecular-weight Aβ oligomers, with the brain total lipid extract (BTLE) membrane resulted in accelerated Aβ fibrillogenesis on the membrane surface. Importantly, the fibrillogenesis did not affect integrity of the membrane. In contrast, small-size (SS) Aβ oligomers, corresponding to low-molecular-weight Aβ oligomers, created pores and then disintegrated the BTLE membrane. Both forms of the Aβ oligomers changed nanomechanical properties of the membrane by decreasing its Young's modulus by ∼45%. Our results demonstrated that both forms of Aβ oligomers induce the neurotoxic effect on the brain cells but their action toward the membrane differs significantly.
淀粉样蛋白 β，Aβ(1-42)，是老年斑的组成部分，存在于阿尔茨海默病患者的大脑中，是导致疾病病理后果的主要嫌疑犯之一。在此，我们直接观察到 Aβ 对类脑模型膜的活性，并证明这种活性强烈依赖于 Aβ 寡聚物的大小。原子力显微镜成像的 PeakForce 定量纳米力学映射模式显示，与高分子量 Aβ 寡聚物相对应的大尺寸（LS）Aβ 寡聚物与脑总脂质提取物（BTLE）膜的相互作用导致 Aβ 在膜表面上加速纤维原纤维形成。重要的是，纤维原纤维形成不会影响膜的完整性。相比之下，小尺寸（SS）Aβ 寡聚物，对应于低分子量 Aβ 寡聚物，形成孔，然后破坏 BTLE 膜。这两种形式的 Aβ 寡聚物通过将膜的杨氏模量降低约 45%来改变膜的纳米力学性能。我们的结果表明，这两种形式的 Aβ 寡聚物都对脑细胞产生神经毒性作用，但它们对膜的作用有很大的不同。
