Direct observation of poloxamer 188 insertion into lipid monolayers

Direct observation of poloxamer 188 insertion into lipid monolayers
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DOI:
10.1016/s0006-3495(02)75499-4
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发表时间:
2002-03-01
影响因子:
3.4
通讯作者:
Lee, KYC
Lee, KYC
中科院分区:
生物学3区
文献类型:
--
作者:
Maskarinec, SA;Hannig, J;Lee, KYC

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P188是一种聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)形式的三嵌段共聚物,有助于密封电穿孔的细胞膜,阻止细胞内物质从受损细胞中泄漏。为了探索P188和细胞膜之间相互作用的性质,我们构建了一个模型系统,评估P188插入脂质单层的能力。同时使用朗缪尔等温线和荧光显微镜测量,我们发现,P188改变的单分子膜的相行为和形态。P188插入二棕榈酰磷脂酰胆碱和二棕榈酰磷脂酰甘油单分子层的表面压力等于或低于22 mN/m,在30 ℃;该压力对应于P188在纯水亚相上获得的最大表面压力。两种磷脂的类似结果表明,P188插入不受头基静电的影响。由于正常双层的等效表面压力为30 mN/m的量级,因此P188插入在22 mN/m以上的缺乏进一步表明泊洛沙姆选择性地吸附到电穿孔膜的受损部分中,从而使其作用局部化。还发现P188在高表面压力下被“挤出”单层,这表明当膜恢复时细胞摆脱泊洛沙姆的机制。
P188, a triblock copolymer of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) helps seal electroporated cell membranes, arresting the leakage of intracellular materials from the damaged cells. To explore the nature of the interaction between P188 and cell membranes, we have constructed a model system that assesses the ability of P188 to insert into lipid monolayers. Using concurrent Langmuir isotherm and fluorescence microscopy measurements, we find that P188 changes the phase behavior and morphology of the monolayers. P188 inserts into both dipalmitoylphosphatidlycholine and dipalmitoylphosphatidylglycerol monolayers at surface pressures equal to and lower than similar to22 mN/m at 30degreesC; this pressure corresponds to the maximal surface pressure attained by P188 on a pure water subphase. Similar results for the two phospholipids indicate that P188 insertion is not influenced by headgroup electrostatics. Because the equivalent surface pressure of a normal bilayer is on the order of 30 mN/m, the lack of P188 insertion above 22 mN/m further suggests the poloxamer selectively adsorbs into damaged portions of electroporated membranes, thereby localizing its effect. P188 is also found to be "squeezed out" of the monolayers at high surface pressures, suggesting a mechanism for the cell to be rid of the poloxamer when the membrane is restored.