Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, California 93106, United States.
Langmuir. 2012 Jul 17;28(28):10495-503. doi: 10.1021/la301181b. Epub 2012 Jun 6.
Environmentally responsive materials (i.e., materials that respond to changes in their environment with a change in their properties or structure) are attracting increasing amounts of interest. We recently designed and synthesized a series of cleavable multivalent lipids (CMVLn, with n = 2-5 being the number of positive headgroup charges at full protonation) with a disulfide bond in the linker between their cationic headgroup and hydrophobic tails. The self-assembled complexes of the CMVLs and DNA are a prototypical environmentally responsive material, undergoing extensive structural rearrangement when exposed to reducing agents. We investigated the structural evolution of CMVL-DNA complexes at varied complex composition, temperature, and incubation time using small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS). A related lipid with a stable linker, TMVL4, was used as a control. In a nonreducing environment, CMVL-DNA complexes form the lamellar (L(α)(C)) phase, with DNA rods sandwiched between lipid bilayers. However, new self-assembled phases form when the disulfide linker is cleaved by dithiothreitol or the biologically relevant reducing agent glutathione. The released DNA and cleaved CMVL headgroups form a loosely organized phase, giving rise to a characteristic broad SAXS correlation profile. CMVLs with high headgroup charge also form condensed DNA bundles. Intriguingly, the cleaved hydrophobic tails of the CMVLs reassemble into tilted chain-ordered L(β') phases upon incubation at physiological temperature (37 °C), as indicated by characteristic WAXS peaks. X-ray scattering further reveals that two of the three phases (L(βF), L(βL), and L(βI)) constituting the L(β') phase coexist in these samples. The described system may have applications in lipid-based nanotechnologies.
环境响应材料（即对环境变化做出响应并改变其性质或结构的材料）越来越受到关注。我们最近设计并合成了一系列具有二硫键的可裂解多价脂质（CMVLn，其中 n 为完全质子化时阳离子头基的正电荷数），其阳离子头基和疏水尾部之间的连接子中存在二硫键。CMVL 与 DNA 自组装复合物是一种典型的环境响应材料，当暴露于还原剂时会发生广泛的结构重排。我们使用小角 X 射线散射（SAXS）和广角 X 射线散射（WAXS）研究了不同复合物组成、温度和孵育时间下 CMVL-DNA 复合物的结构演变。使用具有稳定连接子的相关脂质 TMVL4 作为对照。在非还原环境中，CMVL-DNA 复合物形成层状（L(α)(C)）相，DNA 棒夹在双层脂质之间。然而，当二硫键连接子被二硫苏糖醇或生物相关还原剂谷胱甘肽裂解时，会形成新的自组装相。释放的 DNA 和裂解的 CMVL 头基形成松散组织的相，导致特征性的宽 SAXS 相关分布。具有高头基电荷的 CMVL 还形成浓缩的 DNA 束。有趣的是，CMVL 的裂解疏水尾部在生理温度（37°C）下孵育时会重新组装成倾斜链有序的 L(β') 相，这由特征性的 WAXS 峰表明。X 射线散射进一步表明，构成 L(β') 相的三个相（L(βF)、L(βL)和 L(βI)）中的两个在这些样品中共存。该描述的系统可能在基于脂质的纳米技术中有应用。
