Adhesion and hemifusion of cytoplasmic myelin lipid membranes are highly dependent on the lipid composition.

Adhesion and hemifusion of cytoplasmic myelin lipid membranes are highly dependent on the lipid composition.
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DOI:
10.1016/j.bbamem.2011.10.015
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发表时间:
2012-03
影响因子:
3.4
通讯作者:
Israelachvili, Jacob N.
Israelachvili, Jacob N.
中科院分区:
生物学3区
文献类型:
--
作者:
Banquy, Xavier;Kristiansen, Kai;Lee, Dong Woog;Israelachvili, Jacob N.

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我们报告的影响,钙离子的粘附和半融合机制的模型支持髓鞘脂质双层膜的不同脂质组成。如在我们先前的研究中,使用的脂质组合物模拟"健康"和"疾病样"(实验性自身免疫性脑脊髓炎,EAE)膜。我们的研究结果表明,作为膜分离距离的函数的相互作用力很好地描述了一个通用的模型,也(特别是)包括从疏水暴露(内部)部分的双层所产生的疏水相互作用。该模型能够捕获触发半融合事件发生的机械不稳定性,并突出了疏水相互作用在膜融合中的主要作用。脂质组成对髓鞘脂质双层之间的融合机制和粘附力的影响可以概括如下:在无钙缓冲液中,健康的膜不存在任何粘附或半融合的迹象,而患病的膜容易半融合。添加2 mM钙有利于独立于其组成的膜的粘附和半融合,但在这两个过程中涉及的机制是不同的:健康的双层系统地提出了更强的粘附力和更低的能量障碍融合相比,患病的双层。这些结果对于理解髓鞘相关疾病如多发性硬化中的病变发展(脱髓鞘、肿胀、空泡化和/或囊泡形成)及其与髓鞘膜中脂质结构域形成的关系特别相关。
We report the effects of calcium ions on the adhesion and hemifusion mechanisms of model supported myelin lipid bilayer membranes of differing lipid composition. As in our previous studies, the lipid compositions used mimic “healthy” and “diseased-like” (experimental autoimmune encephalomyelitis, EAE) membranes. Our results show that the interaction forces as a function of membrane separation distance are well described by a generic model that also (and in particular) includes the hydrophobic interaction arising from the hydrophobically exposed (interior) parts of the bilayers. The model is able to capture the mechanical instability that triggers the onset of the hemifusion event, and highlights the primary role of the hydrophobic interaction in membrane fusion. The effects of lipid composition on the fusion mechanism, and the adhesion forces between myelin lipid bilayers, can be summarized as follow: in calcium-free buffer, healthy membranes do not present any signs of adhesion or hemifusion, while diseased membranes hemifuse easily. Addition of 2 mM calcium favors adhesion and hemifusion of the membranes independently of their composition, but the mechanisms involved in the two processes were different: healthy bilayers systematically presented stronger adhesion forces and lower energy barriers to fusion compared to diseased bilayers. These results are of particular relevance for understanding lesion development (demyelination, swelling, vacuolization and/or vesiculation) in myelin associated diseases such as multiple sclerosis and its relationship to lipid domain formation in myelin membranes.
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