The effect of polyethylene glycol-modified lipids on the interaction of HIV-1 derived peptide-dendrimer complexes with lipid membranes
The effect of polyethylene glycol-modified lipids on the interaction of HIV-1 derived peptide-dendrimer complexes with lipid membranes
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DOI：
10.1016/j.bbamem.2016.09.005
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发表时间：
2016-12-01
影响因子：
3.4
通讯作者：
Hianik, Tibor
中科院分区：
文献类型：
--
作者：
Melikishvili, Sophie;Poturnayova, Alexandra;Hianik, Tibor
在这项研究中，树枝状大分子被用作向树突状细胞递送HIV多肽的替代方法。我们研究了由多阴离子HIV多肽Nef和阳离子碳硅烷树枝状大分子(CBD)形成的树枝状网络与模型脂膜-大单层囊泡(LuV)、朗缪尔单层和含有不同摩尔比的两性离子1，2-二肉豆蔻酰甘油-3-磷胆碱(DMPC)和1，2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(聚乙二醇2000)的支撑脂膜(SBLM)的相互作用(DSPE-PEG2000)。在我们的实验中，脂膜代表了细胞质膜的模型。聚乙二醇化的脂类被用来模拟构成细胞膜外层小叶的糖萼。聚乙二醇化脂质的存在提高了狼疮膜脂双层的相变温度，降低了比体积和绝热可压缩性。荧光各向异性研究表明，与两性离子DMPC囊泡相比，聚乙二醇化LuV具有更高的脂质有序性和更低的流动性。BAM实验表明，树枝状聚合物与单分子膜的相互作用伴随着聚集体的形成。这一结论也被sBLMS的AFM成像所证实。我们已经证明树突网络与脂膜相互作用于所有类型的脂类成分。此外，与聚乙二醇化的脂膜相比，阳离子树枝状大分子/肽复合体与脂单分子膜、囊泡和sBLM的相互作用更强。聚乙二醇化脂质浓度的增加使这种相互作用变得更弱。(C)2016爱思唯尔B.V.保留所有权利。
In this study, dendrimers have been purposed as an alternative approach for delivery of HIV peptides to dendritic cells. We have investigated the interaction of dendriplexes formed from polyanionic HIV peptide Nef and cationic carbosilane dendrimer (CBD) with model lipid membranes-large unilamellar vesicles (LUVs), Langmuir mono layers and supported lipid membranes (sBLMs) containing various molar ratio of zwitterionic 1,2-dimyristoylsn-glycero-3-phosphocholine (DMPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) -2000] (DSPE-PEG(2000)). In our experiments, the lipid membranes represented the model of the plasma membrane of the cell. PEGylated lipids were used in order to model glycocalyx which constitutes the outer leaflet of cellular membranes. The presence of PEGylated lipids resulted in an increase of the phase transition temperature of the lipid bilayer of LUVs, in a decrease of specific volume and adiabatic compressibility. Fluorescence anisotropy study suggests that PEGylated LUVs possessed higher lipid order and decreased fluidity when compared to zwitterionic DMPC vesicles. The interaction of dendriplexes with monolayers was accompanied by the formation of the aggregates as revealed by BAM experiments. This conclusion has been confirmed also by AFM imaging of sBLMs. We have demonstrated that dendriplexes interact with lipid membranes for all types of lipid composition. Moreover, the stronger interaction of cationic dendrimer/peptide complexes with lipid monolayers, vesicles and sBLMs was observed for membranes composed of zwitterionic lipids than for PEGylated lipid membranes. Increased concentration of PEGylated lipids made this interaction weaker. (C) 2016 Elsevier B.V. All rights reserved.