Laboratory of Food Process Engineering, ETH Zürich , Schmelzbergstrasse 9, 8092 Zürich, Switzerland.
Laboratory for Neutron Scattering and Imaging, Paul Scherrer Institute , 5232 Villigen PSI, Switzerland.
Langmuir. 2017 Aug 29;33(34):8533-8544. doi: 10.1021/acs.langmuir.7b01370. Epub 2017 Aug 16.
Cholesterol (Chol-OH) and its conjugates are powerful molecules for engineering the physicochemical and magnetic properties of phospholipid bilayers in bicelles. Introduction of aminocholesterol (3β-amino-5-cholestene, Chol-NH) in bicelles composed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and the thulium-ion-chelating phospholipid 1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylene triaminepentaacetate (DMPE-DTPA/Tm) results in unprecedented high magnetic alignments by selectively tuning the magnetic susceptibility Δχ of the bilayer. However, little is known on the underlying mechanisms behind the magnetic response and, more generally, on the physicochemical forces governing a Chol-NH doped DMPC bilayer. We tackled this shortcoming with a multiscale bottom-up comparative investigation of Chol-OH and Chol-NH mixed with DMPC. First, simplified monolayer models on a Langmuir trough were employed to compare the two steroid molecules at various contents in DMPC. In a second step, a molecular dynamics (MD) simulation allowed for a more representative model of the bicelle bilayer while monitoring the amphiphiles and their interactions on the molecular level. In a final step, we moved away from the models and investigated the effect of temperature on the structure and magnetic alignment of Chol-NH doped bicelles by SANS. The DMPC/steroid monolayer studies showed that Chol-OH induces a larger condensation effect than Chol-NH at steroid contents of 16 and 20 mol %. However, this tendency was inversed at steroid contents of 10, 30, and 40 mol %. Although the MD simulation with 16 mol % steroid revealed that both compounds induce a liquid-ordered state in DMPC, the bilayer containing Chol-NH was much less ordered than the analogous system containing Chol-OH. Chol-NH underwent significantly more hydrogen bonding interactions with neighboring DMPC lipids than Chol-OH. It seems that, by altering the dynamics of the hydrophilic environment of the bicelle, Chol-NH changes the crystal field and angle of the phospholipid-lanthanide DMPE-DTPA/Tm complex. These parameters largely determine the magnetic susceptibility Δχ of the complex, explaining the SANS results, which show significant differences in magnetic alignment of the steroid doped bicelles. Highly magnetically alignable DMPC/Chol-NH/DMPE-DTPA/Tm (molar ratio 16:4:5:5) bicelles were achieved up to temperatures of 35 °C before a thermoreversible rearrangement into nonalignable vesicles occurred. The results confirm the potential of Chol-NH doped bicelles to act as building blocks for the development of the magnetically responsive soft materials of tomorrow.
胆固醇（Chol-OH）及其共轭物是用于工程磷脂双层膜物理化学和磁性质的有力分子在双微脂粒中。在由 1,2-二肉豆蔻酰基-sn-甘油-3-磷酸胆碱（DMPC）和铥离子螯合磷脂 1,2-二肉豆蔻酰基-sn-甘油-3-磷酸乙醇胺二乙三胺五乙酸酯（DMPE-DTPA/Tm）组成的双微脂粒中引入氨基胆固醇（3β-氨基-5-胆甾烯，Chol-NH），通过选择性调节双层膜的磁化率Δχ，导致前所未有的高磁取向。然而，对于磁响应背后的基本机制，以及更普遍地，对于控制 Chol-NH 掺杂 DMPC 双层膜的物理化学力，知之甚少。我们通过对 Chol-OH 和 Chol-NH 与 DMPC 混合的多尺度自下而上的比较研究来解决这一缺点。首先，在 Langmuir 渡槽上使用简化的单层模型来比较两种甾醇分子在不同 DMPC 含量下的情况。在第二步中，分子动力学（MD）模拟允许对双微脂粒双层膜进行更具代表性的模型，同时在分子水平上监测两亲物及其相互作用。在最后一步，我们离开了模型，并通过小角中子散射（SANS）研究了温度对 Chol-NH 掺杂双微脂粒结构和磁取向的影响。DMPC/甾醇单层研究表明，Chol-OH 在甾醇含量为 16 和 20 mol%时比 Chol-NH 引起更大的凝聚效应。然而，这种趋势在甾醇含量为 10、30 和 40 mol%时被逆转。尽管含有 16 mol%甾醇的 MD 模拟表明，这两种化合物都在 DMPC 中诱导出液体有序状态，但含有 Chol-NH 的双层膜比含有 Chol-OH 的类似系统无序得多。Chol-NH 与相邻 DMPC 脂质发生的氢键相互作用明显多于 Chol-OH。似乎通过改变双微脂粒亲水性环境的动力学，Chol-NH 改变了磷脂-镧系元素 DMPE-DTPA/Tm 配合物的晶体场和角度。这些参数在很大程度上决定了配合物的磁化率Δχ，解释了 SANS 结果，这些结果显示了甾醇掺杂双微脂粒在磁取向方面的显著差异。高达 35°C 的温度下，成功实现了高磁取向的 DMPC/Chol-NH/DMPE-DTPA/Tm（摩尔比 16:4:5:5）双微脂粒，然后发生热可逆重排为非取向囊泡。结果证实了 Chol-NH 掺杂双微脂粒作为开发未来磁性响应软材料的构建块的潜力。
