Department of Chemistry and Chemical Biology, Physical Chemistry I - Biophysical Chemistry, TU Dortmund University, Otto Hahn Str. 4a, D-44221 Dortmund, Germany.
Institute of Organic Chemistry, University of Münster, Corrensstraße 40, 48149 Münster, Germany.
Langmuir. 2021 Oct 19;37(41):11996-12006. doi: 10.1021/acs.langmuir.1c01565. Epub 2021 Oct 7.
Archaeal lipids have harvested biomedical and biotechnological interest because of their ability to form membranes with low permeability and enhanced temperature and pressure stability. Because of problems in isolating archaeal lipids, chemical synthesis appears to be a suitable means of producing model lipids that mimic the biological counterparts. Here, we introduce a new concept: we synthesized bipolar alkylated imidazolium salts of different chain lengths (BIm10-32) and studied their structure and lyotropic phase behavior. Furthermore, mixtures of the bolalipid analogues with phospholipid model biomembranes of diverse complexity were studied. DSC, fluorescence and FTIR spectroscopy, confocal fluorescence microscopy, DLS, SAXS, and TEM were used to reveal changes in lipid phase behavior, fluidity, the lipid's conformational order, and membrane morphology over a wide range of temperatures and for selected pressures. It could be shown that the long-chain BImN32 can form monolayer sheets. Integrated in phospholipid membranes, it reveals a fluidizing effect. Here, the two polar head groups, connected by a long alkyl chain, enable the integration into the bilayer. Interestingly, addition of BImN32 to fluid DPPC liposomes increased the lipid packing markedly, rendering the membrane system more stable at higher temperatures. The membrane system is also stable against compression as indicated by the high-pressure stability of the system, mimicking an archaeal lipid-like behavior. BImN32 incorporation into raft-like anionic model biomembranes led to marked changes in lateral membrane organization, topology, and fusogenicity of the membrane. Overall, it was found that long-chain imidazolium-based bolalipid analogues can help adjust membrane's biophysical properties, while the imidazolium headgroup provides the ability for crucial electrostatic interaction for vesicle fusion or selective interaction with membrane-related signaling molecules and polypeptides in a synthetically tractable manner. The results obtained may help to develop new approaches for rational design of extremophilic bolalipid-based liposomes for various applications, including delivery of drugs and vaccines.
由于其形成具有低渗透性和增强的温度和压力稳定性的膜的能力，古菌脂质引起了生物医学和生物技术的兴趣。由于古菌脂质的分离问题，化学合成似乎是生产模拟生物对应物的模型脂质的合适方法。在这里，我们引入了一个新概念：我们合成了不同链长的双极性烷基化咪唑鎓盐（BIm10-32），并研究了它们的结构和溶致相行为。此外，还研究了 bolalipid 类似物与不同复杂性的磷脂模型生物膜的混合物。使用 DSC、荧光和 FTIR 光谱、共聚焦荧光显微镜、DLS、SAXS 和 TEM 揭示了在很宽的温度范围内和选定的压力下脂质相行为、流动性、脂质构象有序性和膜形态的变化。结果表明，长链 BImN32 可以形成单层片。整合到磷脂膜中时，它显示出流体化作用。在这里，两个极性头基通过长烷基链连接，使其能够整合到双层中。有趣的是，将 BImN32 添加到流体 DPPC 脂质体中会显著增加脂质堆积，从而使膜系统在较高温度下更稳定。该膜系统在高压下也稳定，模拟了古菌脂质样行为。BImN32 掺入筏状阴离子模型生物膜中会导致膜的侧向组织、拓扑结构和融合性发生明显变化。总体而言，发现长链基于咪唑鎓的 bolalipid 类似物可以帮助调节膜的生物物理性质，而咪唑鎓头基提供了关键静电相互作用的能力，用于囊泡融合或与膜相关的信号分子和多肽的选择性相互作用，以实现合成上的可操作性。获得的结果可能有助于开发基于 bolalipid 的脂质体的合理设计的新方法，用于各种应用，包括药物和疫苗的递送。
