Du H, Chandaroy P, Hui S W
Biophysics Department, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Biochim Biophys Acta. 1997 Jun 12;1326(2):236-48. doi: 10.1016/s0005-2736(97)00027-8.
Monolayers of dipalmitoyl-phosphatidylethanolamine (DPPE) mixing with various mole percentages of distearoyl-phosphatidylethanolamine (DSPE)-conjugated poly-(ethylene glycol) (PEG m.w. 750-5000) were deposited on DPPE-coated glass surfaces by the Langmuir-Blodgett method. Increasing percentages of grafted PEG in these supported lipid surfaces increasingly inhibit the adsorption of bovine serum albumin (BSA), laminin, and fibronectin. Increasing percentages of grafted PEG also inhibit the adhesion of erythrocytes, lymphocytes, and macrophages to these supported lipid surfaces. The adsorption of proteins on lipid coated glass surfaces were assayed by the fluorescence of FITC-labelled proteins. Cell adhesion was measured mainly by microscopic counting. The concentration of PEG-grafted lipids required for the inhibition of erythrocyte adhesion decreases with increasing molecular weight of the grafted PEG. The inhibitory effects are strongly dependent on the graft density of PEG at low concentrations, but weakly dependent on graft density at higher concentrations. For DSPE-PEG5000, the change of graft density dependency occurs approximately at the complete coverage of the lipid surface by the grafted polymer in the mushroom conformation (0.7 mol%), and the transition to partial brush conformation. The change-overs become less distinctive for grafted PEG of lower molecular weights, probably due to the failure of strictly mushroom and brush models of the polymer. The relative inhibitory efficiency is protein or cell dependent. The implication on the function of stealth liposomes is discussed.
通过朗缪尔-布洛杰特法将二棕榈酰磷脂酰乙醇胺(DPPE)与不同摩尔百分比的二硬脂酰磷脂酰乙醇胺(DSPE)共轭聚乙二醇(PEG,分子量750 - 5000)混合形成的单层膜沉积在涂有DPPE的玻璃表面上。这些支撑脂质表面上接枝PEG的百分比增加,对牛血清白蛋白(BSA)、层粘连蛋白和纤连蛋白的吸附抑制作用增强。接枝PEG百分比的增加也抑制红细胞、淋巴细胞和巨噬细胞对这些支撑脂质表面的黏附。通过异硫氰酸荧光素(FITC)标记蛋白的荧光测定脂质包被玻璃表面上蛋白质的吸附。细胞黏附主要通过显微镜计数来测量。抑制红细胞黏附所需的PEG接枝脂质浓度随接枝PEG分子量的增加而降低。在低浓度时,抑制作用强烈依赖于PEG的接枝密度,但在高浓度时弱依赖于接枝密度。对于DSPE - PEG5000,接枝密度依赖性的变化大约发生在接枝聚合物以蘑菇构象完全覆盖脂质表面(0.7摩尔%)并转变为部分刷状构象时。对于较低分子量的接枝PEG,这种转变变得不那么明显,这可能是由于聚合物的严格蘑菇和刷状模型不成立。相对抑制效率取决于蛋白质或细胞。文中讨论了其对隐形脂质体功能的影响。