Structural Evolution of Environmentally Responsive Cationic Liposome-DNA Complexes with a Reducible Lipid Linker
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2979274
- author
- Shirazi, Rahau S. ; Ewert, Kai K. ; Silva, Bruno LU ; Leal, Cecilia ; Li, Youli and Safinya, Cyrus R.
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Langmuir
- volume
- 28
- issue
- 28
- pages
- 10495 - 10503
- publisher
- The American Chemical Society (ACS)
- external identifiers
-
- wos:000306441100023
- scopus:84863926852
- pmid:22616637
- 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
- 2016-04-01 10:55:32
- date last changed
- 2022-01-26 03:45:58
@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 (ACS)}},
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}},
doi = {{10.1021/la301181b}},
volume = {{28}},
year = {{2012}},
}