The Alzheimer's disease amyloid-β peptide affects the size-dynamics of raft-mimicking Lo domains in GM1-containing lipid bilayers.
The Alzheimer's disease amyloid-β peptide affects the size-dynamics of raft-mimicking Lo domains in GM1-containing lipid bilayers.
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阿尔茨海默氏病淀粉样蛋白-β 肽影响含有 GM1 的脂质双层中模拟筏 Lo 结构域的大小动力学。
DOI：
10.1039/c8sm01636d
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发表时间：
2018
期刊：
影响因子：
3.4
通讯作者：
M. Seigneuret
中科院分区：
文献类型：
--
作者：
Galya Staneva;N. Puff;S. Stanimirov;Todor Tochev;M. Angelova;M. Seigneuret
阿尔茨海默病（Alzheimer's disease，AD）的特征是β淀粉样肽（amyloid-β peptide，Aβ）的过量产生，在含有神经节苷脂GM 1的筏微区的影响下，A β形成纤维。含有GM 1的模拟筏的人工液体有序（Lo）结构域增强淀粉样蛋白-β聚合。其他实验表明，在GM 1存在下，Aβ优选与非筏状液体无序（Ld）相结合，而不是与Lo相结合。本文研究了Aβ（1-42）与含GM 1的双相Lo-Ld巨囊泡的相互作用。荧光共定位实验证实Aβ（1-42）优先结合Ld相。利用模拟纳微畴筏状聚结的光诱导亚稳分解研究了Aβ（1-42）对Lo-Ld尺寸动力学的影响。Aβ影响粗化相的动力学和所得微区的尺寸。该效应取决于哪一相占多数：当Lo微区在Ld相内形成时，在Aβ（1-42）存在下，它们的生长速率变慢并且它们的最终尺寸变小，而当Ld微区在Lo相中形成时，生长速率变快并且最终尺寸变大。使用探针Laurdan对大囊泡进行的荧光测量表明，在存在或不存在GM 1的情况下，Aβ（1-42）结合分别增加或减少Ld相的堆积。因此，Aβ对旋节分解的不同影响被解释为是由于该肽对GM 1调节的Lo-Ld线张力的不同影响。Aβ对结构域动力学的这种调节作用对于AD信号转导障碍中的脂筏以及Aβ纤维化可能是重要的。
Alzheimer's disease (AD) is characterized by the overproduction of the amyloid-β peptide (Aβ) which forms fibrils under the influence of raft microdomains containing the ganglioside GM1. Raft-mimicking artificial liquid ordered (Lo) domains containing GM1 enhance amyloid-β polymerization. Other experiments suggest that Aβ binds preferably to the non-raft liquid disordered (Ld) phase rather than to the Lo phase in the presence of GM1. Here, the interaction of Aβ(1-42) with GM1-containing biphasic Lo-Ld giant vesicles was investigated. Fluorescence colocalisation experiments confirm that Aβ(1-42) binds preferentially to the Ld phase. The effect of Aβ(1-42) on the Lo-Ld size dynamics was studied using photoinduced spinodal decomposition which mimics the nanodomain-microdomain raft coalescence. Aβ affects the kinetics of the coarsening phase and the size of the resulting microdomains. The effect depends on which phase is in a majority: when the Lo microdomains are formed inside an Ld phase, their growth rate becomes slower and their final size smaller in the presence of Aβ(1-42), whereas when the Ld microdomains are formed inside an Lo phase, the growth rate becomes faster and the final size larger. Fluorimetric measurements on large vesicles using the probe Laurdan indicate that Aβ(1-42) binding respectively increases or decreases the packing of the Ld phase in the presence or absence of GM1. The differential effects of Aβ on spinodal decomposition are accordingly interpreted as resulting from distinct effects of the peptide on the Lo-Ld line tension modulated by GM1. Such modulating effect of Aβ on domain dynamics could be important for lipid rafts in signaling disorders in AD as well as in Aβ fibrillation.
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影响因子：
13.6
作者：
Carquin M;D'Auria L;Pollet H;Bongarzone ER;Tyteca D
通讯作者：
Tyteca D
DOI：
10.1016/j.bbalip.2008.09.002
发表时间：
2008-11
影响因子：
4.8
作者：
Goni, Felix M.;Alonso, Alicia;Bagatolli, Luis A.;Brown, Rhoderick E.;Marsh, Derek;Prieto, Manuel;Thewalt, Jenifer L.
通讯作者：
Thewalt, Jenifer L.
影响因子：
3.4
作者：
Veatch, SL;Keller, SL
通讯作者：
Keller, SL
阿尔茨海默病。
影响因子：
5.7
作者：
Roses,AD
通讯作者：
Roses,AD