Maintaining the integrity of cell membranes is indispensable for cellular viability. Poloxamer 188 (P188), a poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO–PPO–PEO) triblock copolymer with a number-average molecular weight of 8700 g/mol and containing 80% by mass PEO, protects cell membranes from various external injuries and has the potential to be used as a therapeutic agent in diverse applications. The membrane protection mechanism associated with P188 is intimately connected with how this block copolymer interacts with the lipid bilayer, the main component of a cell membrane. Here, we report the distribution of P188 in a model lipid bilayer comprising 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) using neutron reflectivity (NR) and atomic force microscopy (AFM). We also investigated the association of a PEO homopolymer (PEO8.4K; M_n = 8400 g/mol) that does not protect living cell membranes. These experiments were conducted following incubation of a 4.5 mmol/L polymer solution in a buffer that mimics physiological conditions with supported POPC bilayer membranes followed by washing with the aqueous medium. In contrast to previous reports, which dealt with P188 and PEO in salt-free solutions, both P188 and PEO8.4K penetrate into the inner portion of the lipid bilayer as revealed by NR, with approximately 30% by volume occupancy across the membrane without loss of bilayer structural integrity. These results indicate that PEO is the chemical moiety that principally drives P188 binding to bilayer membranes. No defects or phase-separated domains were observed in either P188- or PEO8.4K-incubated lipid bilayers when examined by AFM, indicating that polymer chains mingle homogeneously with lipid molecules in the bilayer. Remarkably, the breakthrough force required for penetration of the AFM tip through the bilayer membrane is unaffected by the presence of the large amount of P188 and PEO8.4K.

中文翻译：

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脂质双层中PEO-PPO-PEO嵌段共聚物和PEO均聚物的空间分布。

维持细胞膜的完整性对于细胞活力是必不可少的。泊洛沙姆188（P188），聚环氧乙烷-b-聚环氧丙烷-b数均分子量为8700 g / mol的PEO-PPO-PEO三嵌段共聚物，其PEO质量分数为80％，可保护细胞膜免受各种外部伤害，并有潜力用作在多种应用中的治疗剂。与P188相关的膜保护机制与该嵌段共聚物与脂质双分子层（细胞膜的主要成分）的相互作用密切相关。在这里，我们报告使用中子反射率（NR）和原子力显微镜（AFM）在包含1-棕榈酰基-2-油酰基-甘油3-磷酸胆碱（POPC）的模型脂质双层中P188的分布。我们还研究了PEO均聚物（PEO8.4K; M _n= 8400 g / mol），不能保护活细胞膜。在将4.5 mmol / L聚合物溶液在模拟生理条件的缓冲液中与支持的POPC双层膜一起孵育后，用水性介质洗涤，然后进行这些实验。与以前的报道（在无盐溶液中处理P188和PEO）相反，NR揭示P188和PEO8.4K都渗透到脂质双层的内部，整个膜的体积占有率约为30％，而不会损失双层结构完整性。这些结果表明，PEO是主要驱动P188结合到双层膜上的化学部分。用AFM检查时，在P188-或PEO8.4K孵育的脂质双层中均未观察到缺陷或相分离的结构域，表明聚合物链与双层中的脂质分子均匀混合。值得注意的是，大量P188和PEO8.4K的存在不会影响AFM尖端穿透双层膜所需的穿透力。