Impact of Acyl Chain Mismatch on the Formation and Properties of Sphingomyelin-Cholesterol Domains.
Impact of Acyl Chain Mismatch on the Formation and Properties of Sphingomyelin-Cholesterol Domains.
复制标题
酰基链错配对鞘磷脂-胆固醇结构域的形成和性质的影响。
DOI：
10.1016/j.bpj.2019.09.025
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
J. Peter
中科院分区：
文献类型：
--
作者：
Nyholm;Thomas K. M.; Engberg;Oskar; Hautala;Victor; Tsuchikawa;Hiroshi; Lin;Kai-Lan; Murata;Michio; Slotte;J. Peter
在由不饱和（低凝胶-液相转变温度（Tm））磷脂、饱和（高Tm）磷脂和胆固醇组成的三元脂质双分子层中，横向分离和横向结构域的形成是众所周知的现象。横向结构域的形成已被证明受到磷脂酰基链不饱和和长度差异的影响。最近，我们还发现胆固醇与双分子层中高低磷脂的不同相互作用可以促进磷脂分离。现在，我们研究了磷脂-胆固醇相互作用及其在由不同酰基链长度的不同不饱和磷脂酰胆碱（PCs）、n -棕榈酰- d-红鞘磷脂（PSM）和胆固醇组成的三元双分子层中的侧向分离作用。利用氘核磁共振光谱，我们确定了PSM如何受到周围PC环境中酰基链组成的影响，并将其与不同PC环境中胆固醇三烯醇（一种荧光胆固醇类似物）对PSM的亲和力联系起来。反式parinaric酸的时间分辨荧光测量和Förster共振能量转移实验的结果表明，胆固醇对磷脂的相对亲和力决定了甾醇促进结构域形成的程度。从Förster共振能量转移、氘核磁共振和差示扫描量热的结果可以清楚地看出，胆固醇也影响了结构域的热稳定性和富psm结构域内外的有序度。本研究结果表明，胆固醇对低颞叶磷脂和高颞叶磷脂的亲和力以及低颞叶磷脂和高颞叶磷脂的相互作用影响了复杂双分子层的横向结构和结构域性质。我们设想类似的效应也有助于更复杂的生物膜的横向异质性。
Lateral segregation and the formation of lateral domains are well-known phenomena in ternary lipid bilayers composed of an unsaturated (low gel-to-liquid phase transition temperature (Tm)) phospholipid, a saturated (high-Tm) phospholipid, and cholesterol. The formation of lateral domains has been shown to be influenced by differences in phospholipid acyl chain unsaturation and length. Recently, we also showed that differential interactions of cholesterol with low- and high-Tmphospholipids in the bilayer can facilitate phospholipid segregation. Now, we have investigated phospholipid-cholesterol interactions and their role in lateral segregation in ternary bilayers composed of different unsaturated phosphatidylcholines (PCs) with varying acyl chain lengths,N-palmitoyl-D-erythro-sphingomyelin (PSM), and cholesterol. Using deuterium NMR spectroscopy, we determined how PSM was influenced by the acyl chain composition in surrounding PC environments and correlated this with the affinity of cholestatrienol (a fluorescent cholesterol analog) for PSM in the different PC environments. Results from a combination of time-resolved fluorescence measurements oftrans-parinaric acid and Förster resonance energy transfer experiments showed that the relative affinity of cholesterol for phospholipids determined the degree to which the sterol promoted domain formation. From Förster resonance energy transfer, deuterium NMR, and differential scanning calorimetry results, it was clear that cholesterol also influenced both the thermostability of the domains and the degree of order in and outside the PSM-rich domains. The results of this study have shown that the affinity of cholesterol for both low-Tmand high-Tmphospholipids and the effects of low- and high-Tmphospholipids on each other influence both lateral structure and domain properties in complex bilayers. We envision that similar effects also contribute to lateral heterogeneity in even more complex biological membranes.