Kenworthy A K, Hristova K, Needham D, McIntosh T J
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Biophys J. 1995 May;68(5):1921-36. doi: 10.1016/S0006-3495(95)80369-3.
The interactive properties of liposomes containing phospholipids with covalently attached poly(ethylene glycol) (PEG-lipids) are of interest because such liposomes are being developed as drug delivery vehicles and also are ideal model systems for measuring the properties of surface-grafted polymers. For bilayers containing PEG-lipids with PEG molecular weights of 350, 750, 2000, and 5000, pressure-distance relations have been measured by X-ray diffraction analysis of liposomes subjected to known applied osmotic pressures. The distance between apposing bilayers decreased monotonically with increasing applied pressure for each concentration of a given PEG-lipid. Although for bilayers containing PEG-350 and PEG-750 the contribution of electrostatic repulsion to interbilayer interactions was significant, for bilayers containing PEG-2000 and PEG-5000 the major repulsive pressure between bilayers was a steric pressure due to the attached PEG. The range and magnitude of this steric pressure increased both with increasing PEG-lipid concentration and PEG size, and the extension length of the PEG from the bilayer surface at maximum PEG-lipid concentration depended strongly on the size of the PEG, being less than 35 A for PEG-750, and about 65 A for PEG-2000 and 115 A for PEG-5000. The measured pressure-distance relations have been modeled in terms of current theories (deGennes, 1987; Milner et al., 1988b) for the steric pressure produced by surface-grafted polymers, as modified by us to take into account the effects of polymer polydispersity and the possibility that, at low grafting densities, polymers from apposing bilayers surfaces can interpenetrate or interdigitate. No one theoretical scheme is sufficient to account for all the experimental results. However, for a given pressure regime, PEG-lipid size, and PEG-lipid surface density, the appropriately modified theoretical treatment gives a reasonable fit to the pressure-distance data.
含有共价连接聚乙二醇（PEG - 脂质）的磷脂的脂质体的相互作用特性备受关注，因为此类脂质体正被开发用作药物递送载体，并且也是用于测量表面接枝聚合物性质的理想模型系统。对于含有分子量为350、750、2000和5000的PEG - 脂质的双层膜，通过对承受已知外加渗透压的脂质体进行X射线衍射分析，测量了压力 - 距离关系。对于给定PEG - 脂质的每种浓度，相对双层膜之间的距离随外加压力增加而单调减小。尽管对于含有PEG - 350和PEG - 750的双层膜，静电排斥对双层膜间相互作用的贡献显著，但对于含有PEG - 2000和PEG - 5000的双层膜，双层膜之间的主要排斥压力是由于连接的PEG产生的空间位阻压力。这种空间位阻压力的范围和大小随PEG - 脂质浓度和PEG大小的增加而增加，并且在最大PEG - 脂质浓度下PEG从双层膜表面的伸展长度强烈依赖于PEG的大小，对于PEG - 750小于35 Å，对于PEG - 2000约为65 Å，对于PEG - 5000为115 Å。已根据当前关于表面接枝聚合物产生的空间位阻压力的理论（德热纳，1987；米尔纳等人，1988b）对测量的压力 - 距离关系进行了建模，我们对该理论进行了修改，以考虑聚合物多分散性的影响以及在低接枝密度下相对双层膜表面的聚合物可能相互渗透或相互交错的可能性。没有一种理论方案足以解释所有实验结果。然而，对于给定的压力范围、PEG - 脂质大小和PEG - 脂质表面密度，经过适当修改的理论处理能合理拟合压力 - 距离数据。
