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胆固醇和褪黑素对模拟临床前构象疾病的模型膜所引入的结构变化。

Structural changes introduced by cholesterol and melatonin to the model membranes mimicking preclinical conformational diseases.

作者信息

Murugova Tatiana, Ivankov Oleksandr, Ermakova Elena, Kondela Tomáš, Hrubovčák Pavol, Skoi Vadim, Kuklin Alexander, Kučerka Norbert

机构信息

Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, Dubna, Russia.

出版信息

Gen Physiol Biophys. 2020 Mar;39(2):135-144. doi: 10.4149/gpb_2019054.

DOI:10.4149/gpb_2019054
PMID:32329441
Abstract

The structure and dynamics of membranes depend on many external and internal factors that in turn determine their biological functions. One of the widely accepted and studied characteristics of biomembranes is their fluidity. We research a simple system with variable fluidity tweakable via its composition. The addition of cholesterol is employed to increase the order of lipid chains, thus decreasing the membrane fluidity, while melatonin is shown to elevate the chain disorder, thus also the membrane fluidity. We utilize the densitometric measurements to show a shift of studied systems closer or further from the gel-to-fluid phase transition. The structural changes represented by changes to membrane thickness are evaluated from small angle neutron scattering. Finally, we look at the ability of the two additives to control the interactions between membrane and amyloid-beta peptides. Our results suggest that fluidizing effect of melatonin can promote an insertion of peptide within the membrane interior. Intriguingly, the latter structure relates possibly to an Alzheimer's disease preventing mechanism postulated in the case of melatonin.

摘要

膜的结构和动力学取决于许多外部和内部因素,而这些因素反过来又决定了它们的生物学功能。生物膜被广泛接受和研究的特征之一是其流动性。我们研究了一个简单的系统,其流动性可通过组成进行调节。添加胆固醇用于增加脂质链的有序性,从而降低膜的流动性,而褪黑素则显示可提高链的无序性,进而增加膜的流动性。我们利用密度测量来表明所研究的系统离凝胶-流体相转变更近或更远的变化。从小角中子散射评估由膜厚度变化所代表的结构变化。最后,我们研究了这两种添加剂控制膜与β-淀粉样肽之间相互作用的能力。我们的结果表明,褪黑素的流化作用可以促进肽插入膜内部。有趣的是,后一种结构可能与褪黑素情况下假定的阿尔茨海默病预防机制有关。

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