Hsu Wei-Long, Chen Hsin-Lung, Liou Willisa, Lin Hsien-Kuang, Liu Wen-Liang
Department of Chemical Engineering, National Tsing Hua University, Hsin-Chu 30013, Taiwan.
Langmuir. 2005 Oct 11;21(21):9426-31. doi: 10.1021/la051863e.
Polyanionic DNA binds to cationic lipids to form electrostatic complexes exhibiting rich self-assembled structures. These types of complexes have been considered as a nonviral carrier in gene therapy and as a template for nanostructure construction. For the latter application where biocompatibility is not the key issue, replacement of cationic lipid by cationic surfactant is advantageous due to the wide availability of surfactant. Here we report the self-assembly behavior of the complexes of DNA with a cationic surfactant, dodecyltrimethylammonium bromide (DTAB), mixed with a neutral lipid, dioleoylphosphatidylethanolamine (DOPE), in fully hydrated state as a function of DTAB-to-DNA base pair molar ratio (x), DOPE-to-DTAB molar ratio (m) and temperature. The binary complexes of DNA with DTAB microphase separated to form hydrophilic and hydrophobic domains without long-range order. Incorporating DOPE into the complexes effectively strengthened the hydrophobic interaction and hence promoted the formations of long-range ordered mesophases, including a condensed multilamellar phase (L(alpha)(c)) at small to intermediate m (m </= approximately 4) and an inverted hexagonal phase (H(II)(c)) at large m (m > approximately 6). The lyotropic mesophase transition with respect to the change of m was properly predicted by a formula for calculating the packing parameter of amphiphile mixture. In addition to the lyotropic transition, an unusual thermotropic order-order transition (OOT) between L(alpha)(c) and H(II)(c) phases was revealed for the isoelectric complex with m = 3. This OOT was thermally reversible and was postulated to be driven by the reduction of the effective headgroup area due to the release of trapped water molecules.
聚阴离子DNA与阳离子脂质结合形成具有丰富自组装结构的静电复合物。这类复合物在基因治疗中被视为非病毒载体，也被用作纳米结构构建的模板。对于生物相容性不是关键问题的后一种应用，用阳离子表面活性剂替代阳离子脂质是有利的，因为表面活性剂来源广泛。在此，我们报道了在完全水合状态下，DNA与阳离子表面活性剂十二烷基三甲基溴化铵（DTAB）以及中性脂质二油酰磷脂酰乙醇胺（DOPE）形成的复合物的自组装行为，该行为是DTAB与DNA碱基对摩尔比（x）、DOPE与DTAB摩尔比（m）以及温度的函数。DNA与DTAB形成的二元复合物发生微相分离，形成无长程有序的亲水和疏水区域。将DOPE掺入复合物中有效地增强了疏水相互作用，从而促进了长程有序中间相的形成，包括在较小至中等m值（m≤约4）时形成的凝聚多层相（L(α)(c)）和在较大m值（m＞约6）时形成的反相六角相（H(II)(c)）。通过计算两亲混合物堆积参数的公式可以合理预测关于m变化的溶致中间相转变。除了溶致转变外，还发现对于m = 3的等电复合物，在L(α)(c)和H(II)(c)相之间存在不寻常的热致有序-有序转变（OOT）。这种OOT是热可逆的，据推测是由于被困水分子的释放导致有效头基面积减小而驱动的。
