Structural Evolution of Environmentally Responsive Cationic Liposome鈥揇NA Complexes with a Reducible Lipid Linker
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- 作者：Rahau S. Shirazi ; Kai K. Ewert ; Bruno F. B. Silva ; Cecilia Leal ; Youli Li ; Cyrus R. Safinya
- 刊名：Langmuir
- 出版年：2012
- 出版时间：July 17, 2012
- 年：2012
- 卷：28
- 期：28
- 页码：10495-10503
- 全文大小：527K
- 年卷期：v.28,no.28(July 17, 2012)
- ISSN：1520-5827
文摘
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鈥? 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鈥揇NA 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鈥揇NA complexes form the lamellar (L伪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尾鈥?/sub> phases upon incubation at physiological temperature (37 掳C), as indicated by characteristic WAXS peaks. X-ray scattering further reveals that two of the three phases (L尾F, L尾L, and L尾I) constituting the L尾鈥?/sub> phase coexist in these samples. The described system may have applications in lipid-based nanotechnologies.