Efremova N V, Bondurant B, O'Brien D F, Leckband D E
Department of Chemical Engineering, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Biochemistry. 2000 Mar 28;39(12):3441-51. doi: 10.1021/bi992095r.
Poly(ethylene glycol) (PEG)-stabilized liposomes were recently shown to exhibit differences in cell uptake that were linked to the liposome charge. To determine the differences and similarities between charged and uncharged PEG-decorated liposomes, we directly measured the forces between two supported, neutral bilayers with terminally grafted PEG chains. The measurements were performed with the surface force apparatus. The force profiles were similar to those measured with negatively charged PEG conjugates of 1, 2-distearoyl-sn-glycero-3-phosphatidyl ethanolamine (DSPE), except that they lacked the longer ranged electrostatic repulsion observed with the charged compound. Theories for simple polymers describe the forces between end-grafted polymer chains on neutral bilayers. The force measurements were complemented by surface plasmon resonance studies of protein adsorption onto these layers. The lack of electrostatic forces reduced the adsorption of positively charged proteins and enhanced the adsorption of negatively charged ones. The absence of charge also allowed us to determine how membrane charge and the polymer grafting density independently affect protein adsorption on the coated membranes. Such studies suggest the physical basis of the different interactions of charged and uncharged liposomes with proteins and cells.
聚乙二醇(PEG)稳定的脂质体最近被证明在细胞摄取方面存在差异,这些差异与脂质体电荷有关。为了确定带电荷和不带电荷的PEG修饰脂质体之间的异同,我们直接测量了两个带有末端接枝PEG链的支撑中性双层膜之间的力。测量是使用表面力仪进行的。力曲线与用1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺(DSPE)的带负电荷的PEG缀合物测量的曲线相似,只是它们缺乏带电荷化合物所观察到的较长程的静电排斥。简单聚合物的理论描述了中性双层膜上末端接枝聚合物链之间的力。通过表面等离子体共振研究蛋白质在这些层上的吸附对力测量进行了补充。静电力的缺乏减少了带正电荷蛋白质的吸附,并增强了带负电荷蛋白质的吸附。电荷的缺失还使我们能够确定膜电荷和聚合物接枝密度如何独立影响蛋白质在包被膜上的吸附。此类研究揭示了带电荷和不带电荷的脂质体与蛋白质和细胞不同相互作用的物理基础。