α,α′-trehalose 6,6′-dibehenate in non-phospholipid-based liposomes enables direct interaction with trehalose, offering stability during freeze-drying
α,α′-trehalose 6,6′-dibehenate in non-phospholipid-based liposomes enables direct interaction with trehalose, offering stability during freeze-drying
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DOI：
10.1016/j.bbamem.2008.01.013
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发表时间：
2008-05-01
影响因子：
3.4
通讯作者：
Nielsen, Hanne Morck
中科院分区：
文献类型：
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作者：
Christensen, Dennis;Kirby, Daniel;Nielsen, Hanne Morck
海藻糖是一种众所周知的生物结构保护剂，如脂质体和蛋白质在冷冻干燥过程中，但今天仍然有一个关于其作用机制的大争论。在之前的实验中，我们已经证明海藻糖能够在冷冻干燥期间保护由阳离子二甲基双十八烷基铵（DDA）和海藻糖6，6-二山嵛酸酯（TDB）组成的非磷脂基脂质体佐剂（命名为CAF 01）[D.克里斯滕森角，澳-地福格德岛罗森克兰兹Nielsen，P. Andersen，E.M. Agger，海藻糖在冷冻干燥过程中保留DDA/TDB脂质体及其佐剂作用，Biochim。Biophys.生物工程学报1768（2007）2120-2129]。此外，发现TDB是海藻糖稳定作用所必需的。在本文中，我们使用Langmuir-Blodgett技术表明，在水-脂质界面处存在的高浓度的TDB导致约67 mN/m的表面压力，而纯DDA在压缩状态下约为47 mN/m。这表明TDB的海藻糖头部基团与水之间的吸引力大于DDA的季铵头部基团与水之间的吸引力。此外，将海藻糖添加到含有少量TDB的DDA单层中也增加了表面压力，这在不存在TDB的情况下没有观察到。这表明，即使是少量的海藻糖在TDB上存在于水-脂质界面处的自由海藻糖与脂质体表面相关联，推测是通过TDB的海藻糖头基与自由海藻糖分子之间的氢键。因此，对于CAF 01，TDB组分不仅稳定阳离子脂质体并增强免疫应答，而且通过与TDB的头部基团直接相互作用促进海藻糖的冷冻/冻干保护。此外，结果表明，海藻糖必须与脂质体表面直接相互作用，才能在冻干过程中提供保护。(C)2008 Elsevier B. V.保留所有权利。
Trehalose is a well known protector of biostructures like liposomes and proteins during freeze-drying, but still today there is a big debate regarding its mechanism of action. In previous experiments we have shown that trehalose is able to protect a non-phospholipid-based liposomal adjuvant (designated CAF01) composed of the cationic dimethyldioctadecylammonium (DDA) and trehalose 6,6-dibehenate (TDB) during freeze-drying [D. Christensen, C. Foged, I. Rosenkrands, H.M. Nielsen, P. Andersen, E.M. Agger, Trehalose preserves DDA/TDB liposomes and their adjuvant effect during freeze-drying, Biochim. Biophys. Acta, Biomembr. 1768 (2007) 2120-2129]. Furthermore it was seen that TDB is required for the stabilizing effect of trehalose. Herein, we show using the Langmuir-Blodgett technique that a high concentration of TDB present at the water-lipid interface results in a surface pressure around 67 mN/m as compared to that of pure DDA which is approximately 47 mN/m in the compressed state. This indicates that the attractive forces between the trehalose head group of TDB and water are greater than those between the quaternary ammonium head group of DDA and water. Furthermore, addition of trehalose to a DDA monolayer containing small amounts of TDB also increases the surface pressure, which is not observed in the absence of TDB. This suggests that even small amounts of trehalose groups on TDB present at the water-lipid interface associate free trehalose to the liposome surface, presumably by hydrogen bonding between the trehalose head groups of TDB and the free trehalose molecules. Hence, for CAF01 the TDB component not only stabilizes the cationic liposomes and enhances the immune response but also facilitates the cryo-/lyoprotection by trehalose through direct interaction with the head group of TDB. Furthermore the results indicate that direct interaction with liposome surfaces is necessary for trehalose to enable protection during freeze-drying. (C) 2008 Elsevier B.V. All rights reserved.