Acyl Chain Length and Saturation Modulate Interleaflet Coupling in Asymmetric Bilayers: Effects on Dynamics and Structural Order

Acyl Chain Length and Saturation Modulate Interleaflet Coupling in Asymmetric Bilayers: Effects on Dynamics and Structural Order
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DOI:
10.1016/j.bpj.2012.10.033
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发表时间:
2012-12-05
影响因子:
3.4
通讯作者:
London, Erwin
London, Erwin
中科院分区:
生物学3区
文献类型:
--
作者:
Chiantia, Salvatore;London, Erwin

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关于膜结构和功能的一个长期存在的问题是双层膜的内部和外部小叶的物理性质相互耦合的程度。利用我们最近开发的方法制备了不对称囊泡,研究了囊泡内小叶含有磷脂酰胆碱(PC),外小叶含有鞘磷脂(SM)的偶联性。以PC和SM酰基链结构为函数,监测了横向扩散和膜序的耦合。脑SM外小叶的存在降低了外小叶的外侧扩散,但对二油酰基PC组成的内小叶的外侧扩散影响不大(即扩散在两个小叶中仅弱耦合),但对由一个饱和和一个油酰基链组成的PC组成的内小叶的外侧扩散却大大降低了(即扩散在这些情况下是强耦合的)。此外,引入具有长交叉酰基链的外小叶乳SM或人工合成的c24∶0 SM后,外小叶扩散减少,而由二油基PC组成的内小叶扩散也大大减少,表明强偶联。引人注目的是,几项实验表明,SM诱导的外小叶的有序并没有反映在内小叶中脂质有序的增加,即内小叶和外小叶膜有序之间没有可检测到的耦合。我们提出了一个模型,如何横向扩散可以耦合在相反的小叶和讨论这可能会影响膜的功能。
A long-standing question about membrane structure and function is the degree to which the physical properties of the inner and outer leaflets of a bilayer are coupled to one another. Using our recently developed methods to prepare asymmetric vesicles, coupling was investigated for vesicles containing phosphatidylcholine (PC) in the inner leaflet and sphingomyelin (SM) in the outer leaflet. The coupling of both lateral diffusion and membrane order was monitored as a function of PC and SM acyl chain structure. The presence in the outer leaflet of brain SM, which decreased outer-leaflet lateral diffusion, had little effect upon lateral diffusion in inner leaflets composed of dioleoyl PC (i.e., diffusion was only weakly coupled in the two leaflets) but did greatly reduce lateral diffusion in inner leaflets composed of PC with one saturated and one oleoyl acyl chain (i.e., diffusion was strongly coupled in these cases). In addition, reduced outer-leaflet diffusion upon introduction of outer-leaflet milk SM or a synthetic C24:0 SM, both of which have long interdigitating acyl chains, also greatly reduce diffusion of inner leaflets composed of dioleoyl PC, indicative of strong coupling. Strikingly, several assays showed that the ordering of the outer leaflet induced by the presence of SM was not reflected in increased lipid order in the inner leaflet, i.e., there was no detectable coupling between inner and outer leaflet membrane order. We propose a model for how lateral diffusion can be coupled in opposite leaflets and discuss how this might impact membrane function.