CEA/DSV/iBiTec-S, UMR CNRS 8221, SB2SM, F-91191 Gif sur Yvette Cedex, France.
Langmuir. 2013 Mar 19;29(11):3677-87. doi: 10.1021/la304524a. Epub 2013 Mar 6.
Amphiphilic cyclodextrins, with a cholesterol anchor (βChol) or an aspartic acid moiety esterified by two lauryl acyl chains (βDLC), were designed to combine the inclusion ability of the cyclodextrin cavity with the carrier properties of model membranes. Their insertion in phosphatidylcholine bilayers induces a marked lateral phase separation into a pure lipid phase and a cyclodextrin-rich phase (LCD), organized as a 2D cyclodextrin network stabilized by intermolecular hydrogen bonds between the saccharide headgroups at the membrane surface (Roux, M.; Perly, B.; Djedaïni-Pilard, F. Self-Assemblies of Amphiphilic Cyclodextrins. Eur. Biophys. J.2007, 36, 861-867). We have replaced the dilauryl anchor by a single lauryl chain grafted onto a leucine residue, giving monolauryl-β-cyclodextrin (βMLC), which readily inserts into bilayers of chain-deuterated DMPC-d27. The removal of one lauryl acyl chain leads to a dynamic membrane insertion of this new cyclodextrin derivative, with significant lipid exchange on the deuterium NMR time scale between a loosely packed cyclodextrin-enriched phase (L'CD) and free lipid regions, yielding broadened two-component NMR spectra. Like the LCD phases, the cyclodextrin-enriched L'CD regions remain (partially) fluid below the DMPC-d27 main fluid-to-gel transition but do not undergo a clear transition toward a gel state, as observed at 14.5 °C in the LCD phase induced by the dilauryl derivative. Partially fluid lipids of the βMLC-induced L'CD phase coexist with pure lipids in the Pβ' gel phase with possible exchange between them until all of the lipids undergo a transition toward an Lβ' gel state at around 7 °C. Trimethylated monolauryl-β-cyclodextrins induce only an ordering of the lipid acyl chains just above the main transition, without any lateral phase separation. Similar chain ordering is also observed within the βMLC-induced L'CD phase as a consequence of the deep membrane insertion of the monolauryl nonmethylated cyclodextrin derivative.
两亲性环糊精，带有胆固醇锚（βChol）或由两条月桂酰链酯化的天冬氨酸部分（βDLC），旨在将环糊精腔的包合能力与模型膜的载体性质结合起来。它们插入磷脂双层中会引起明显的横向相分离，形成纯脂质相和富含环糊精的相（LCD），该相组织为二维环糊精网络，由分子间氢键稳定，这些氢键存在于膜表面的糖基头部之间（Roux，M.；Perly，B.；Djedaïni-Pilard，F.。两亲性环糊精的自组装。Eur. Biophys. J.2007，36，861-867）。我们用接枝在亮氨酸残基上的单个月桂酰链取代了双月桂酰锚，得到单月桂酰-β-环糊精（βMLC），它很容易插入链氘代 DMPC-d27 的双层中。去除一个月桂酰酰基链会导致这种新的环糊精衍生物的动态膜插入，在氘 NMR 时间尺度上，在松散堆积的富含环糊精的相（L'CD）和游离脂质区域之间会发生显著的脂质交换，产生展宽的双组分 NMR 谱。与 LCD 相类似，富含环糊精的 L'CD 区在 DMPC-d27 的主要流态-凝胶转变以下仍然保持（部分）流体状态，但不会像在由双月桂酰衍生物诱导的 LCD 相中观察到的那样向凝胶态发生明显的转变。βMLC 诱导的 L'CD 相中部分流体脂质与 Pβ'凝胶相中纯脂质共存，并可能在它们之间交换，直到所有脂质在 7°C 左右向 Lβ'凝胶态转变。三甲基化单月桂酰-β-环糊精仅在上主转变上方引起脂质酰链的有序排列，而没有任何横向相分离。在单月桂酰非甲基化环糊精衍生物的深膜插入的影响下，在βMLC 诱导的 L'CD 相中也观察到类似的链有序排列。
