Molecular substructure of the liquid-ordered phase formed by sphingomyelin and cholesterol: sphingomyelin clusters forming nano-subdomains are a characteristic feature

Molecular substructure of the liquid-ordered phase formed by sphingomyelin and cholesterol: sphingomyelin clusters forming nano-subdomains are a characteristic feature
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鞘磷脂和胆固醇形成的液体有序相的分子亚结构:形成纳米亚域的鞘磷脂簇是一个特征

DOI:
10.1007/s12551-022-00967-1
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发表时间:
2022
影响因子:
--
通讯作者:
London Erwin
London Erwin
中科院分区:
--
文献类型:
--
作者:
Murata Michio;Matsumori Nobuaki;Kinoshita Masanao;London Erwin

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作为脂筏的一种模型,鞘磷脂(SM)和胆固醇(CHO)在双层膜中形成的液体有序相(LO)长期以来一直受到生物物理研究者的关注。新的途径和方法使人们对LO结构域结构的分子基础有了更好的了解。本文综述了由SM/不饱和磷脂/CHO组成的模型膜体系的研究,表明LO相含有SM基纳米域(或纳米亚域)。一些LO相的性质可以归因于这些纳米结构域。一些研究表明,纳米结构域包含密集堆积的SM分子,在生理温度下形成一位数纳米尺寸的凝胶相样亚结构域。位于LO相的CHO和不饱和脂类很可能集中在亚区之间的边界。这些亚区在饱和磷脂酰胆碱(PC)分子形成的LO相中很难检测到,这表明它们被SM特有的同亲相互作用所强烈稳定,例如SM酰胺基团之间的作用。LO相的这一模型得到了使用二氢SM(被认为比SM具有更强的同亲相互作用)的实验、使用SM的2位和3位具有与SM相反的立体化学的SM的对映体的研究以及对含有LO-脂的脂双层的一些分子动力学(MD)模拟的支持。纳米凝胶亚域似乎在控制生物膜的膜组织和功能方面起着重要的作用。
As a model of lipid rafts, the liquid-ordered (Lo) phase formed by sphingomyelin (SM) and cholesterol (Cho) in bilayer membranes has long attracted the attention of biophysics researchers. New approaches and methodologies have led to a better understanding of the molecular basis of the Lo domain structure. This review summarizes studies on model membrane systems consisting of SM/unsaturated phospholipid/Cho implying that the Lo phase contains SM-based nanodomains (or nano-subdomains). Some of the Lo phase properties may be attributed to these nanodomains. Several studies suggest that the nanodomains contain clustered SM molecules packed densely to form gel-phase-like subdomains of single-digit nanometer size at physiological temperatures. Cho and unsaturated lipids located in the Lo phase are likely to be concentrated at the boundaries between the subdomains. These subdomains are not readily detected in the Lo phase formed by saturated phosphatidylcholine (PC) molecules, suggesting that they are strongly stabilized by homophilic interactions specific to SM, e.g., between SM amide groups. This model for the Lo phase is supported by experiments using dihydro-SM, which is thought to have stronger homophilic interactions than SM, as well as by studies using the enantiomer of SM having opposite stereochemistry to SM at the 2 and 3 positions and by some molecular dynamics (MD) simulations of lipid bilayers containing Lo-lipids. Nanosized gel subdomains seem to play an important role in controlling membrane organization and function in biological membranes.
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