Institute of Pharmaceutical and Biomedical Science, Johannes Gutenberg-University Mainz, 55128 Mainz, Germany.
Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Cells. 2020 Sep 29;9(10):2213. doi: 10.3390/cells9102213.
Lipid exchange among biological membranes, lipoprotein particles, micelles, and liposomes is an important yet underrated phenomenon with repercussions throughout the life sciences. The premature loss of lipid molecules from liposomal formulations severely impacts therapeutic applications of the latter and thus limits the type of lipids and lipid conjugates available for fine-tuning liposomal properties. While cholesterol derivatives, with their irregular lipophilic surface shape, are known to readily undergo lipid exchange and interconvert, e.g., with serum, the situation is unclear for lipids with regular, linear-shaped alkyl chains. This study compares the propensity of fluorescence-labeled lipid conjugates of systematically varied lengths to migrate from liposomal particles consisting mainly of egg phosphatidyl choline 3 (EPC3) and cholesterol into biomembranes. We show that dialkyl glyceryl lipids with chains of 18-20 methylene units are inherently stable in liposomal membranes. In contrast, C16 lipids show some lipid exchange, albeit significantly less than comparable cholesterol conjugates. Remarkably, the C18 chain length, which confers noticeable anchor stability, corresponds to the typical chain length in biological membranes.
生物膜、脂蛋白颗粒、胶束和脂质体之间的脂质交换是一种重要但被低估的现象，对生命科学的各个领域都有影响。脂质体配方中脂质分子的过早损失严重影响了后者的治疗应用，从而限制了可用于微调脂质体性质的脂质和脂质缀合物的类型。虽然胆固醇衍生物具有不规则的亲脂性表面形状，已知它们很容易进行脂质交换和相互转化，例如与血清，对于具有规则线性烷基链的脂质情况尚不清楚。本研究比较了荧光标记的脂质缀合物的迁移倾向，这些脂质缀合物的长度是系统变化的，从主要由蛋黄卵磷脂 3（EPC3）和胆固醇组成的脂质体颗粒进入生物膜。我们表明，具有 18-20 个亚甲基单元的二烷基甘油脂质在脂质体膜中固有稳定。相比之下，C16 脂质表现出一些脂质交换，但明显少于可比的胆固醇缀合物。值得注意的是，赋予明显锚定稳定性的 C18 链长对应于生物膜中的典型链长。
