Nanoscale View of Amyloid Photodynamic Damage
Nanoscale View of Amyloid Photodynamic Damage
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DOI：
10.1021/jacs.9b10632
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发表时间：
2020-01-15
影响因子：
15
通讯作者：
Flors, Cristina
中科院分区：
文献类型：
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作者：
Bondia, Patricia;Torra, Joaquim;Flors, Cristina
时间分辨光谱和纳米级成像的组合已被用于研究选择性光氧化致病聚集体的光催化剂的淀粉样蛋白的复合物结合，以及其照射的后果。相关的原子力显微镜（AFM）和荧光显微镜揭示了拓扑结构依赖的染料结合模型β-乳球蛋白纤维，这也可以解释观察到的差异，他们的光降解反应。我们提供了直接的证据，光敏单线态氧的光催化剂结合淀粉样蛋白纤维的直接检测其近红外磷光。单线态氧在分子水平上的作用带来了纳米级的形态变化，可以用AFM在单纤维水平上观察到。我们还发现了两个α-突触核蛋白突变体对光损伤的不同反应，这可以通过存在对光氧化敏感的氨基酸来合理化。总的来说，我们的研究结果有助于解开一些与高度异质性淀粉样蛋白人群相关的复杂性，并有助于淀粉样蛋白相关疾病的改善光疗策略的发展。
A combination of time-resolved optical spectroscopy and nanoscale imaging has been used to study the complex binding to amyloids of a photocatalyst that selectively photo-oxygenates pathogenic aggregates, as well as the consequences of its irradiation. Correlative atomic force microscopy (AFM) and fluorescence microscopy reveals topography-dependent binding of the dye to model beta-lactoglobulin fibers, which may also explain the observed difference in their response to photodegradation. We provide direct evidence of the photosensitization of singlet oxygen by the photocatalyst bound to amyloid fibers by direct detection of its NIR phosphorescence. The effect of singlet oxygen at the molecular level brings about nanoscale morphological changes that can be observed with AFM at the single-fiber level. We also find differential response of two a-synuclein mutants to photodamage, which can be rationalized by the presence of amino acids susceptible to photo-oxygenation. Overall, our results help to unravel some of the complexity associated with highly heterogeneous amyloid populations and contribute to the development of improved phototherapeutic strategies for amyloid-related disorders.