Xiao Qi, Wang Zhichun, Williams Dewight, Leowanawat Pawaret, Peterca Mihai, Sherman Samuel E, Zhang Shaodong, Hammer Daniel A, Heiney Paul A, King Steven R, Markovitz David M, André Sabine, Gabius Hans-Joachim, Klein Michael L, Percec Virgil
Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6323, United States.
Department of Bioengineering, University of Pennsylvania , Philadelphia, Pennsylvania 19104-6321, United States.
ACS Cent Sci. 2016 Dec 28;2(12):943-953. doi: 10.1021/acscentsci.6b00284. Epub 2016 Dec 5.
Nonlamellar lipid arrangements, including cubosomes, appear in unhealthy cells, e.g., when they are subject to stress, starvation, or viral infection. The bioactivity of cubosomes-nanoscale particles exhibiting bicontinuous cubic structures-versus more common vesicles is an unexplored area due to lack of suitable model systems. Here, glycodendrimercubosomes (GDCs)-sugar-presenting cubosomes assembled from Janus glycodendrimers by simple injection into buffer-are proposed as mimics of biological cubic membranes. The bicontinuous cubic GDC architecture has been demonstrated by electron tomography. The stability of these GDCs in buffer enabled studies on lectin-dependent agglutination, revealing significant differences compared with the vesicular glycodendrimersome (GDS) counterpart. In particular, GDCs showed an increased activity toward concanavalin A, as well as an increased sensitivity and selectivity toward two variants of banana lectins, a wild-type and a genetically modified variant, which is not exhibited by GDSs. These results suggest that cells may adapt under unhealthy conditions by undergoing a transformation from lamellar to cubic membranes as a method of defense.
包括立方液晶相在内的非层状脂质排列出现在不健康的细胞中，例如当细胞受到压力、饥饿或病毒感染时。由于缺乏合适的模型系统，立方液晶相（呈现双连续立方结构的纳米级颗粒）与更常见的囊泡相比的生物活性是一个未被探索的领域。在此，提出了糖树枝状立方液晶相（GDCs）——通过简单注射到缓冲液中由Janus糖树枝状大分子组装而成的含糖立方液晶相——作为生物立方膜的模拟物。通过电子断层扫描证实了双连续立方GDC结构。这些GDCs在缓冲液中的稳定性使得能够进行凝集素依赖性凝集研究，揭示了与囊泡状糖树枝状聚合物囊泡（GDS）对应物相比的显著差异。特别是，GDCs对伴刀豆球蛋白A表现出增强的活性，以及对香蕉凝集素的两种变体（野生型和基因修饰变体）具有更高的敏感性和选择性，而GDSs则不具备这些特性。这些结果表明，细胞可能在不健康条件下通过从层状膜转变为立方膜作为一种防御方法来进行适应。
