Raft domain reorganization driven by short- and long-chain ceramide: A combined AFM and FCS study

Raft domain reorganization driven by short- and long-chain ceramide: A combined AFM and FCS study
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DOI:
10.1021/la7010919
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发表时间:
2007-07-03
期刊:
影响因子:
3.9
通讯作者:
Schwille, Petra
Schwille, Petra
中科院分区:
化学2区
文献类型:
--
作者:
Chiantia, Salvatore;Kahya, Nicoletta;Schwille, Petra

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已知天然存在的长链神经酰胺(Cer)改变生物膜的横向组织。特别是,它们产生参与从细胞凋亡到免疫应答的几个细胞过程的微结构域的改变。为了诱导类似的生物学效应,在体内实验中广泛使用短链Cer来代替其长链类似物。在这项工作中,我们使用的原子力显微镜(AFM)和荧光相关光谱(FCS)相结合的方法来调查的Cer链长度的影响,在脂质双层组成的鞘磷脂,二油酰磷脂酰胆碱,和胆固醇。我们的研究结果表明,只有长链Cer,如C18和C16,能够从液体有序相分离,形成单独的Cerenriched域。相反,短链Cer不形成单独的相,但改变液体有序结构域的物理性质,降低其稳定性和粘度,并扰乱脂质包装。这些差异可能有助于解释长链和短链Cer经常观察到的不同生理效应。
Naturally occurring long-chain ceramides (Cer) are known to alter the lateral organization of biological membranes. In particular, they produce alterations of microdomains that are involved in several cellular processes, ranging from apoptosis to immune response. In order to induce similar biological effects, short-chain Cer are extensively used in in vivo experiments to replace their long-chain analogues. In this work, we used the combined approach of atomic force microscopy (AFM) and fluorescence correlation spectroscopy (FCS) to investigate the effect of Cer chain length in lipid bilayers composed of sphingomyelin, dioleoyl-phosphatidylcholine, and cholesterol. Our results show that only long-chain Cer, like C18 and C16, are able to segregate from the liquid-ordered phase, forming separate Cerenriched domains. Conversely, short-chain Cer do not form a separate phase but alter the physical properties of the liquid-ordered domains, decreasing their stability and viscosity and perturbing the lipid packing. These differences may contribute to the explanation of the different physiological effects that are often observed for the long- and short-chain Cer.