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Structural Evolution of Environmentally Responsive Cationic Liposome-DNA Complexes with a Reducible Lipid Linker

Shirazi, Rahau S.; Ewert, Kai K.; Silva, Bruno LU ; Leal, Cecilia; Li, Youli and Safinya, Cyrus R. (2012) In Langmuir 28(28). p.10495-10503
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... (More)
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-alpha(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-beta, 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-beta F, L-beta L, and L-beta 1) constituting the L-beta. phase coexist in these samples. The described system may have applications in lipid-based nanotechnologies. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Langmuir
volume
28
issue
28
pages
10495 - 10503
publisher
The American Chemical Society
external identifiers
  • wos:000306441100023
  • scopus:84863926852
ISSN
0743-7463
DOI
10.1021/la301181b
language
English
LU publication?
yes
id
91b45862-4a54-45c0-8713-6ec6c8e79544 (old id 2979274)
date added to LUP
2012-08-23 09:03:29
date last changed
2017-11-05 03:21:05
@article{91b45862-4a54-45c0-8713-6ec6c8e79544,
  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-alpha(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-beta, 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-beta F, L-beta L, and L-beta 1) constituting the L-beta. phase coexist in these samples. The described system may have applications in lipid-based nanotechnologies.},
  author       = {Shirazi, Rahau S. and Ewert, Kai K. and Silva, Bruno and Leal, Cecilia and Li, Youli and Safinya, Cyrus R.},
  issn         = {0743-7463},
  language     = {eng},
  number       = {28},
  pages        = {10495--10503},
  publisher    = {The American Chemical Society},
  series       = {Langmuir},
  title        = {Structural Evolution of Environmentally Responsive Cationic Liposome-DNA Complexes with a Reducible Lipid Linker},
  url          = {http://dx.doi.org/10.1021/la301181b},
  volume       = {28},
  year         = {2012},
}