Department of Chemistry, Indian Institute of Technology Bombay, Mumbai 400076, India.
ACS Appl Bio Mater. 2023 Dec 18;6(12):5555-5562. doi: 10.1021/acsabm.3c00748. Epub 2023 Nov 28.
Lipidic adjuvant formulations consisting of immunomodulatory mycobacterial cell wall lipids interact with host cells following administration. The impact of this cross-talk on the host membrane's structure and function is rarely given enough consideration but is imperative to rule out nonspecific perturbation underlying the adjuvant. In this work, we investigated changes in the plasma membranes of live mammalian cells after exposure to mycobacterial mycolic acid (MA) and phenolic glycolipids, two strong candidates for lipidic adjuvant therapy. We found that phenolic glycolipid 1 softened the plasma membrane, lowering membrane tension and stiffness, but MA did not significantly change the membrane characteristics. Further, phenolic glycolipid 1 had a fluidizing impact on the host plasma membrane, increasing the fluidity and the abundance of fluid-ordered-disordered coexisting lipid domains. Notably, lipid diffusion was not impacted. Overall, MA and, to a lesser extent, phenolic glycolipid 1, due to minor disruption of host cell membranes, may serve as appropriate lipids in adjuvant formulations.
脂质佐剂制剂由具有免疫调节作用的分枝杆菌细胞壁脂质组成，在给药后与宿主细胞相互作用。这种细胞间的相互作用对宿主细胞膜的结构和功能的影响很少得到足够的考虑，但为了排除佐剂的非特异性干扰，这是必要的。在这项工作中，我们研究了暴露于分枝杆菌分枝酸（MA）和酚基甘油二脂后活哺乳动物细胞膜的变化，这两种物质是脂质佐剂治疗的强有力候选物。我们发现，酚基甘油二脂 1 使细胞膜变软，降低了膜张力和刚性，但 MA 对膜特性没有显著影响。此外，酚基甘油二脂 1 对宿主质膜具有增溶作用，增加了流动性和共存的有序无序脂质域的丰度。值得注意的是，脂质扩散没有受到影响。总的来说，MA 和在较小程度上的酚基甘油二脂 1 由于对宿主细胞膜的轻微破坏，可能作为佐剂制剂中的合适脂质。
