title: Structural evolution of environmentally responsive cationic liposome-DNA complexes with a reducible lipid linker.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara, California 93106, United States.
authors.forename: Rahau S
authors.initials: RS
authors.lastname: Shirazi
authors.forename: Kai K
authors.initials: KK
authors.lastname: Ewert
authors.forename: Bruno F B
authors.initials: BF
authors.lastname: Silva
authors.forename: Cecilia
authors.initials: C
authors.lastname: Leal
authors.forename: Youli
authors.initials: Y
authors.lastname: Li
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Safinya
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D002417:Cattle; D004247:DNA / Q000737:chemistry*; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D002412:Cations; D008055:Lipids; D008081:Liposomes; D004247:DNA; C427203:calf thymus DNA