Atomic Force Microscopic Analysis of the Effect of Lipid Composition on Liposome Membrane Rigidity.
Atomic Force Microscopic Analysis of the Effect of Lipid Composition on Liposome Membrane Rigidity.
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DOI：
10.1021/acs.langmuir.6b00741
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Yuki Takechi-Haraya;K. Sakai-Kato;Yasuhiro Abe;T. Kawanishi;H. Okuda;Y. Goda
中科院分区：
文献类型：
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作者：
Yuki Takechi-Haraya;K. Sakai-Kato;Yasuhiro Abe;T. Kawanishi;H. Okuda;Y. Goda
脂质体膜的机械刚性通常由膜的弯曲模数来定义，是脂质体稳定性的决定因素之一，但定量的实验数据仍然局限于少数几种脂质体。在这里，我们使用原子力显微镜来研究脂质体在水介质中固定在牛血清白蛋白涂层玻璃上的膜弯曲模数。以下脂类用于脂质体的制备：蛋黄磷脂酰胆碱、二油酰磷脂酰胆碱、氢化大豆磷脂酰胆碱、二棕榈酰磷脂酰胆碱、1，2-二油酰基-3-三甲基氨丙烷、胆固醇和N-(甲氧基甲氧基聚乙二醇酯)2000)-1，2-distearoyl-sn-glycero-3-phosphoethanolamine.通过使用不同组成的脂质体，我们发现膜的热力学相态而不是电势或聚乙二醇改性的脂质体表面修饰是决定弯曲模量的主要因素，其顺序为：固体有序>；液体有序>；液体无序。利用Laurdan荧光探针的广义偏振值，研究了膜的刚性对膜流动性的影响。原子力显微镜分析优于Laurdan方法，特别是在评价氢化大豆磷脂酰胆碱和胆固醇脂质体的膜硬度方面。弯曲模数较大的正电荷脂质体被细胞吸收的效率高于弯曲模数较小的脂质体。这些发现提供了一种定量分析不同脂类组成纳米脂质体的膜硬度的方法，并将有助于控制脂质体的稳定性和临床使用的细胞摄取效率。
Mechanical rigidity of the liposome membrane is often defined by the membrane bending modulus and is one of the determinants of liposome stability, but the quantitative experimental data are still limited to a few kinds of liposomes. Here, we used atomic force microscopy to investigate the membrane bending moduli of liposomes by immobilizing them on bovine serum albumin-coated glass in aqueous medium. The following lipids were used for liposome preparation: egg yolk phosphatidylcholine, dioleoylphosphatidylcholine, hydrogenated soybean phosphatidylcholine, dipalmitoylphosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium-propane, cholesterol, and N-(carbonylmethoxypoly(ethylene glycol) 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine. By using liposomes of various compositions, we showed that the thermodynamic phase state of the membrane rather than the electric potential or liposome surface modification with poly(ethylene glycol) is the predominant determinant of the bending modulus, which decreased in the following order: solid ordered > liquid ordered > liquid disordered. By using the generalized polarization value of the Laurdan fluorescent probe, we investigated membrane rigidity in terms of membrane fluidity. Atomic force microscopic analysis was superior to the Laurdan method, especially in evaluating the membrane rigidity of liposomes containing hydrogenated soybean phosphatidylcholine and cholesterol. Positively charged liposomes with a large bending modulus were taken up by cells more efficiently than those with a small bending modulus. These findings offer a quantitative method of analyzing the membrane rigidity of nanosized liposomes with different lipid compositions and will contribute to the control of liposome stability and cellular uptake efficiency of liposomal formulations intended for clinical use.