The Structure of DNA−Liposome Complexes

Lasiç, Danilo D.; Strey, Helmut H.; Stuart, Marc C. A.; Podgornik, Rudolf; Frederik, Peter M.

doi:10.1021/ja962713g

Cited by 375 publications

(336 citation statements)

References 14 publications

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“…n GC (z) ) 1 2πl B 1 (z + b) 2 (3) DMPC lipids leads to a considerable compression of a membrane and to a concurrent enhancement of the ordering of nonpolar hydrocarbon chains for both DMPC and DMTAP. Furthermore, sodium ions give rise to a reorientation of zwitterionic PC headgroups in the outward direction of the bilayer, which results in a slight increase of the total electrostatic potential across a monolayer.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Monovalent Salt on Cationic Lipid Membranes As Revealed by Molecular Dynamics Simulations

Gurtovenko

Miettinen²,

Karttunen³

et al. 2005

J. Phys. Chem. B

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An atomic-scale understanding of cationic lipid membranes is required for development of gene delivery agents based on cationic liposomes. To address this problem, we recently performed molecular dynamics (MD) simulations of mixed lipid membranes comprised of cationic dimyristoyltrimethylammonium propane (DMTAP) and zwitterionic dimyristoylphosphatidylcholine (DMPC) (Biophys. J. 2004, 86, 3461-3472). Given that salt ions are always present under physiological conditions, here we focus on the effects of monovalent salt (NaCl) on cationic (DMPC/DMTAP) membranes. Using atomistic MD simulations, we found that saltinduced changes in membranes depend strongly on their composition. When the DMTAP mole fraction is small (around 6%), the addition of monovalent salt leads to a considerable compression of the membrane and to a concurrent enhancement of the ordering of lipid acyl chains. That is accompanied by reorientation of phosphatidylcholine headgroups in the outward normal direction and slight changes in electrostatic properties. We attribute these changes to complexation of DMPC lipids with Na + ions which penetrate deep into the membrane and bind to the carbonyl region of the DMPC lipids. In contrast, at medium and high molar fractions of cationic DMTAP (50 and 75%) a substantial positive surface charge density of the membranes prevents the binding of Na + ions, making such membranes almost insensitive to monovalent salt. Finally, we compare our results to the Poisson-Boltzmann theory. With the exception of the immediate vicinity of the bilayer plane, we found excellent agreement with the theory. This is as expected since unlike in the theoretical description the surface is now structured due to its atomic scale nature.

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Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] However, while cationic lipids are nowadays widely used in molecular cell biology, they are still not as efficient as viral vectors. Their further development is hence highly desirable.…”

Section: Introductionmentioning

confidence: 99%

Effect of Monovalent Salt on Cationic Lipid Membranes As Revealed by Molecular Dynamics Simulations

Gurtovenko

Miettinen²,

Karttunen³

et al. 2005

J. Phys. Chem. B

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“…26 While additional experiments are needed to exclude the possibility that a specific DNA-liposome complex structure is essential for successful transfection, data in Figure 2 introduce the possibility that gene expression in the lung obtained by intravenous injection of DNA-liposome complexes may result from free DNAmediated transfection and may not require a special structure of DNA-lipid complexes, as suggested by some previous studies. [27][28][29] While it is evident that free DNA is capable of being taken up and encoded gene is expressed by cells in the lung, more experiments are needed to confirm whether the cells transfected are endothelial cells lining the capillary wall of the lung, as suggested by previous studies using DNA-liposome complexes. 26 It will also be important to know whether cells in other organs can also be efficiently transfected by naked DNA if they are maintained in contact with cells for a prolonged period of time.…”

Section: Figure 6 Persistence Of Transgene Expression Each Mouse Recmentioning

confidence: 99%

Enhanced gene expression in mouse lung by prolonging the retention time of intravenously injected plasmid DNA

Song

Liu

1998

Gene Ther

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The effect of retention time of plasmid DNA in mouse lung cholesterol-based cationic liposomes to retain the plasmid on the level of transgene expression after intravenous DNA in the lung. The level and patterns of gene expression administration was examined. Using CMV driven obtained appeared similar to those seen in animals transexpression system with luciferase gene as a reporter and fected by DNA-liposome complexes. These results sugpreinjection of free cationic liposomes into the animal as gest that prolonging the exposure time of DNA to the target means of manipulating the retention time of plasmid DNA, cells in vivo may be an important strategy in achieving a we demonstrated that naked plasmid DNA is effective in high level of gene expression. Our data also introduce transfecting cells in the lung by intravenous administration.a possibility that the function of cationic liposomes in An increase in DNA retention time in the lung results in a lipoplex-mediated transfection in vivo is to extend the higher level of gene expression. Liposomes composed of interaction time of DNA with the cells. cationic lipids with alkyl chains exhibited better activity than

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“…The limitations of DNA-lipid complexes (lipoplexes) include the low DNA transfection efficiency, particularly in nondividing cells, the heterogeneous size distribution of the particles, and poor reproducibility in some cases. The reasons for these limitations have been studied intensively from a physicochemical viewpoint [1][2][3][4][5][6][7]. The shape of lipoplexes is an important factor affecting transfection efficiency.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the shape parameters of DNA–cationic lipid complexes and model polyelectrolyte–lipid complexes

Sun

Takaoka

et al. 2004

Journal of Colloid and Interface Science

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The Structure of DNA−Liposome Complexes

Cited by 375 publications

References 14 publications

Effect of Monovalent Salt on Cationic Lipid Membranes As Revealed by Molecular Dynamics Simulations

Effect of Monovalent Salt on Cationic Lipid Membranes As Revealed by Molecular Dynamics Simulations

Enhanced gene expression in mouse lung by prolonging the retention time of intravenously injected plasmid DNA

Comparison of the shape parameters of DNA–cationic lipid complexes and model polyelectrolyte–lipid complexes

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