Interaction of poloxamers with liposomes: an isothermal titration calorimetry study.
Interaction of poloxamers with liposomes: an isothermal titration calorimetry study.
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DOI：
10.1021/jp906331m
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发表时间：
2009-11
期刊：
影响因子：
--
通讯作者：
Guohui Wu;Ka Yee C. Lee
中科院分区：
文献类型：
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作者：
Guohui Wu;Ka Yee C. Lee
脂质双层和泊洛沙姆之间的相互作用最近引起了人们的广泛关注，泊洛沙姆对脂质膜完整性的矛盾作用已经被揭示;据报道，泊洛沙姆是有效的密封剂或细胞膜的透化剂，这取决于细胞类型。为了阐明泊洛沙姆-膜相互作用，我们研究了使用等温滴定量热法（ITC）的脂质双层相结构，泊洛沙姆浓度和温度所发挥的作用。我们的研究结果表明，脂质双层相结构在其与泊洛沙姆的相互作用中起着至关重要的作用。发现泊洛沙姆仅分配到流体相而不是凝胶相膜中。此外，由于在升高的温度下泊洛沙姆的膜流动性和疏水性的增强，泊洛沙姆分配到流体相脂质体中随温度增加。我们的ITC结果还指出了泊洛沙姆的饱和浓度，低于该浓度泊洛沙姆可以分配到脂质双层中而不破坏脂质体，高于该浓度泊洛沙姆则将脂质体分解成胶束。为了解决泊洛沙姆在吸附到预先形成的脂质体上后是否通过脂质双层迁移的长期问题，使用两个ITC方案来交叉验证泊洛沙姆在双层中两个小叶上的分布。我们发现，在一个很短的时间尺度（约200分钟）泊洛沙姆分区到外小叶的流体相脂质双层没有太多的相互作用与内小叶。然而，在较长的时间尺度（38小时），他们被发现迁移通过双层，并最终建立一个均匀的分布在膜的内外小叶。
The interaction between lipid bilayers and poloxamers has recently attracted much attention, and contradicting effects of poloxamers have been revealed on the integrity of lipid membranes; poloxamers are reported to be either effective sealants or permeabilizers of cell membranes depending on the cell type. To elucidate poloxamer-membrane interactions, we study the roles played by the lipid bilayer phase structure, poloxamer concentration, and temperature using isothermal titration calorimetry (ITC). Our results indicate that the lipid bilayer phase structure plays a critical role in its interaction with poloxamers. Poloxamers are found to partition only into fluid-phase, not gel-phase, membranes. Moreover, the partitioning of poloxamers into fluid-phase liposomes increases with temperature, owing to the enhancement in both the membrane fluidity and the hydrophobicity of the poloxamer at elevated temperatures. Our ITC results also point to a saturation concentration of poloxamers, below which poloxamers can partition into a lipid bilayer without disrupting liposomes and above which they instead disintegrate liposomes into micelles. To address the long-standing question as to whether poloxamers migrate through the lipid bilayer after their adsorption onto preformed liposomes, two ITC protocols are used to cross-validate the distribution of poloxamers over the two leaflets in the bilayer. We find that on a short timescale (approximately 200 min) poloxamers partition into the outer leaflet of the fluid-phase lipid bilayer without much interactions with the inner leaflet. However, on a longer timescale (38 h), they are found to migrate through the bilayer and eventually establish an even distribution in both the inner and outer leaflets of the membrane.