Biomedical Engineering and Chemical and Biochemical Engineering, Rutgers University, Piscataway, New Jersey 08854, United States.
Langmuir. 2012 Mar 6;28(9):4113-22. doi: 10.1021/la204765r. Epub 2012 Feb 22.
Lateral lipid phase separation of titratable PS or PA lipids and their assembly in domains induced by changes in pH are significant in liposome-based drug delivery: environmentally responsive lipid heterogeneities can be tuned to alter collective membrane properties such as permeability (altering drug release) and surface topography (altering drug carrier reactivity) impacting, therefore, the therapeutic outcomes. At the micrometer scale fluorescence microscopy on giant unilamellar fluid vesicles (GUVs) shows that lowering pH (from 7.0 to 5.0) promotes condensation of titratable PS or PA lipids into beautiful floret-shaped domains in which lipids are tightly packed via hydrogen-bonding and van der Waals interactions. The order of lipid packing within domains increases radially toward the domain center. Lowering pH enhances the lipid packing order, and at pH 5.0 domains appear to be entirely in the solid (gel) phase. Domains phenomenologically comprise a circular "core" cap beyond which interfacial instabilities emerge resembling leaf-like stripes. At pH 5.0 stripes are of almost vanishing Gaussian curvature independent of GUVs' preparation path and in agreement with a general condensation mechanism. Increasing incompressibility of domains is strongly correlated with a larger number of thinner stripes per domain and increasing relative rigidity of domains with smaller core cap areas. Line tension drives domain ripening; however, the final domain shape is a result of enhanced incompressibility and rigidity maximized by domain coupling across the bilayer. Introduction of a transmembrane osmotic gradient (hyperosmotic on the outer lipid leaflet) allows the domain condensation process to reach its maximum extent which, however, is limited by the minimal expansivity of the continuous fluid membrane.
可滴定 PS 或 PA 脂质的侧向脂质相分离及其在 pH 变化诱导的域中的组装在基于脂质体的药物递送中非常重要：环境响应性脂质不均匀性可被调谐以改变集体膜性质，如渗透性（改变药物释放）和表面形貌（改变药物载体反应性），从而影响治疗结果。在微米尺度上，对巨单层流体囊泡（GUV）的荧光显微镜研究表明，降低 pH（从 7.0 降低至 5.0）可促进可滴定 PS 或 PA 脂质凝聚成美丽的小花状结构域，其中脂质通过氢键和范德华相互作用紧密堆积。域内脂质堆积的有序性沿径向向域中心增加。降低 pH 会增强脂质堆积的有序性，并且在 pH 5.0 时，域似乎完全处于固态（凝胶态）。域从现象上包含一个圆形的“核心”帽，超出该帽出现界面不稳定性，类似于叶状条纹。在 pH 5.0 时，条纹的高斯曲率几乎为零，这与 GUV 的制备路径无关，与一般的凝聚机制一致。域的不可压缩性的增加与每个域中的较薄条纹数量增加以及具有较小核心帽面积的域的相对刚性增加强烈相关。线张力驱动域成熟；然而，最终的域形状是增强的不可压缩性和通过双层跨越的域耦合最大化的刚性的结果。引入跨膜渗透梯度（外层脂质小叶的高渗）可允许域凝聚过程达到其最大程度，但这受到连续流体膜的最小扩张性的限制。
