Université Paris-Saclay, Institute for Integrative Biology of the Cell, URA CNRS 9198, F-91191 Gif sur Yvette CEDEX, France.
Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, F-91400 Orsay, France.
J Phys Chem B. 2023 Mar 23;127(11):2475-2487. doi: 10.1021/acs.jpcb.2c07331. Epub 2023 Mar 13.
Small bilayer lipid aggregates such as bicelles provide useful isotropic or anisotropic membrane mimetics for structural studies of biological membranes. We have shown previously by deuterium NMR that a wedge-shaped amphiphilic derivative of trimethyl βcyclodextrin anchored in deuterated DMPC-d27 bilayers through a lauryl acyl chain (TrimβMLC) is able to induce magnetic orientation and fragmentation of the multilamellar membranes. The fragmentation process fully detailed in the present paper is observed with 20% cyclodextrin derivative below 37 °C, where pure TrimβMLC self-assembles in water into large giant micellar structures. After deconvolution of a broad composite H NMR isotropic component, we propose a model where the DMPC membranes are progressively disrupted by TrimβMLC into small and large micellar aggregates depending whether they are extracted from the outer or inner layers of the liposomes. Below the fluid-to-gel transition of pure DMPC-d27 membranes ( = 21.5 °C), the micellar aggregates vanish progressively until complete extinction at 13 °C, with a probable release of pure TrimβMLC micelles leaving lipid bilayers in the gel phase doped with only a small amount of the cyclodextrin derivative. Bilayer fragmentation between and 13 °C was also observed with 10% and 5% of TrimβMLC, with NMR spectra suggesting possible interactions of micellar aggregates with fluid-like lipids of the P ripple phase. No membrane orientation and fragmentation was detected with unsaturated POPC membranes, which are able to accommodate the insertion of TrimβMLC without important perturbation. The data are discussed in relation to the formation of possible DMPC bicellar aggregates such as those known to occur after insertion of dihexanoylphosphatidylcholine (DHPC). These bicelles are in particular associated with similar deuterium NMR spectra exhibiting identical composite isotropic components which were never characterized before.
小双层脂质体（如双脂质体）可提供有用的各向同性或各向异性的膜模拟物，用于生物膜的结构研究。我们之前通过氘 NMR 表明，通过月桂酰链锚定在氘化 DMPC-d27 双层中的三甲基β-环糊精的楔形两亲性衍生物（TrimβMLC）能够诱导多层膜的磁定向和碎片化。本文详细描述了碎片化过程，在低于 37°C 的情况下，20%的环糊精衍生物存在时，该过程可以观察到，此时纯 TrimβMLC 在水中自组装成大的巨型胶束结构。对宽复合 H NMR 各向同性分量进行解卷积后，我们提出了一个模型，其中 DMPC 膜被 TrimβMLC 逐渐破坏成小和大的胶束聚集体，具体取决于它们是从脂质体的外层还是内层提取的。在纯 DMPC-d27 膜的流态到凝胶态转变（=21.5°C）以下，胶束聚集体逐渐消失，直到在 13°C 时完全消失，可能释放出纯 TrimβMLC 胶束，使脂质双层处于凝胶相中，仅掺杂少量环糊精衍生物。在 10%和 5%的 TrimβMLC 存在下，也观察到在 和 13°C 之间的双层碎片化，NMR 谱表明胶束聚集体与 P 纹波相的流体状脂质之间可能存在相互作用。未检测到不饱和 POPC 膜的膜取向和碎片化，这些膜能够在没有重要干扰的情况下容纳 TrimβMLC 的插入。数据与可能的 DMPC 双脂质体聚集体的形成有关，例如在插入二己酰基磷脂酰胆碱（DHPC）后已知会发生的聚集体。这些双脂质体特别与具有相同复合各向同性分量的类似氘 NMR 谱相关联，这些分量以前从未被表征过。
