Max-Planck-Institut für Eisenforschung, 40237, Düsseldorf, Germany.
Forschungszentrum Jülich, 52428, Jülich, Germany.
Sci Rep. 2018 Dec 4;8(1):17615. doi: 10.1038/s41598-018-36110-y.
Amyloid-beta (Ab) proteins play an important role in a number of neurodegenerative diseases. Ab is found in senile plaques in brains of Alzeimer's disease patients. The 42 residues of the monomer form dimers which stack to fibrils gaining several micrometers in length. Using Ab fibrils with C and N marker substitution, we developed an innovative approach to obtain insights to structural and chemical information of the protein. We deposited the modified protein fibrils to pre-sharped aluminium needles with >100-nm apex diameters and, using the position-sensitive mass-to-charge spectrometry technique of atom probe tomography, we acquired the chemically-resolved three dimensional information for every detected ion evaporated in small fragments from the protein. We also discuss the influence of experimental parameters such as pulse energy and pulse frequency of the used Laser beam which lead to differences in the size of the gained fragments, developing the capability of localising metal atom within Ab plaques.
淀粉样蛋白-β (Ab) 蛋白在许多神经退行性疾病中起着重要作用。Ab 存在于阿尔茨海默病患者大脑中的老年斑中。单体的 42 个残基形成二聚体，堆叠成原纤维，长度增加数微米。使用具有 C 和 N 标记取代的 Ab 原纤维，我们开发了一种创新方法来深入了解蛋白质的结构和化学信息。我们将修饰后的蛋白原纤维沉积到具有 >100nm 尖端直径的预锐化铝针上，并使用原子探针断层扫描的位置敏感质荷比质谱技术，我们为从蛋白中蒸发的每个小片段的检测离子获得了化学分辨的三维信息。我们还讨论了实验参数的影响，如激光束的脉冲能量和脉冲频率，这导致获得的片段大小存在差异，从而提高了在 Ab 斑块内定位金属原子的能力。
