DNA-lipid systems. A physical chemistry study · 509 Braz J Med Biol Res 35(5) 2002 DNA-lipid...

Braz J Med Biol Res 35(5) 2002

DNA-lipid systems

DNA-lipid systems. A physicalchemistry study

1Departamento de Química, Universidade de Coimbra, Coimbra, Portugal2Physical Chemistry 1, Center for Chemistry and Chemical Engineering,Lund University, Lund, Sweden

R. Dias1, F. Antunes1,M. Miguel1, S. Lindman2

and B. Lindman2

Abstract

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CorrespondenceB. Lindman

Physical Chemistry 1

Center for Chemistry and

Chemical Engineering

Lund University

P.O. Box 124

221 00 Lund

Sweden

E-mail: mgmiguel@ci.uc.pt orbjorn.lindman@fkem1.lu.se

Presented at the XXX Annual

Meeting of the Brazilian Society

of Biochemistry and Molecular

Biology, Caxambu, MG, Brazil,

May 19-22, 2001.

Research supported by JNICT and

Praxis XXI (PRAXIS/BD/21227/99),

Fundação para a Ciência e Tecnologia

(FCT, Project Sapiens

PCTI/99/QUI/35414), Portugal,

Swedish Research Council for

Engineering Sciences (TFR), and

Center for Amphiphilic Polymers

(CAP), Lund, Sweden.

Received November 5, 2001

Accepted February 26, 2002

Key words� DNA� Cationic surfactants� Catanionic mixtures� Chitosan� Phase behavior� Polyelectrolyte-oppositely

charged surfactant systems

Introduction

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Brazilian Journal of Medical and Biological Research (2002) 35: 509-522ISSN 0100-879X Review

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DNA displays a strong associativebehavior with cationic surfactants

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Thermodynamicskinetics DNA-lipid complex

(genosome)Colloidal and

biologicalstability

Opsonization

ENDOCYTOSIS

LIPID-MEDIATEDPORATION

Intracellulartrafficking

DNA release intocytoplasm

Endosomefusion/disruption

Cell membrane

Protein mRNA

Nucleus Endosome

Cytoplasm

Fusion

Translation

Figure 1. A hypothetical modelof gene transfection. Three pos-sible methods of cell entry areindicated. Reprinted from Ref. 1,with permission.

Cationicliposomes

DNA-lipid systems

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Non-studiedregion

H2ODTAB40%

0.001 0.01 0.1 1 10

[DNA] (mM)

0.001 0.01 0.1 1 10

[DNA] (mM)

Salt addition

Figure 2. A, Schematic represen-tation of the isothermal pseudo-ternary phase diagram for theDNA-dodecyltrimethylammo-nium bromide (DTAB)-water sys-tem. There is a phase separationinto two phases in almost theentire region considered. B, Ex-panded view of the water cor-ner of the system (diamond) in-cluding the DNA-tetradecyltri-methylammonium bromide(TTAB)-water (triangle) and DNA-cetyltrimethylammonium bro-mide (CTAB)-water (circle) sys-tems for comparison. Opensymbols refer to the clear one-phase solutions and filled sym-bols to two-phase samples. C,Phase map for the same threesystems in the presence of 0.1M NaBr. T = 25�C. Redrawnfrom Ref. 11, with permission.

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0.010.01 0.1 1 10 100

[DNA] (mM)

Figure 3.� Same as Figure 2Bwith results on the DNA decyltri-methylammonium bromide(DeTAB)-water (squares) andDNA-octyltrimethylammoniumbromide (OTAB)-water (crosses)systems. The open symbols cor-respond to one-phase solutionsand the filled symbols to two-phase samples. T = 25�C.

DNA-lipid systems

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Attractive ion-ion correlationeffects for DNA in the presenceof multivalent ions

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DNA� Cat� An�� Cat�

DNA� S� An� S�

Figure 4. Pyramid representationof the phase diagram for a sys-tem of solvent (water), DNA saltand surfactant. Four monovalentions are present: DNA- (DNApolyanion), S+ (surfactant cat-ion), An- (simple anion), and Cat+

(simple cation).

Figure 5. The end-to-end dis-tance is shown as a function ofmonomer charge for differentvalences of the counterions. Nosalt was added (N = 80, cm = 5.4mM, and b = 6 Å). Reprintedfrom Ref. 25, with permission.

500 0.5 1.0 1.5

Monomer charge

Monovalent

Divalent

Trivalent

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DNA is compacted by cationicsurfactants

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Figure 6. Fluorescence imagesof T4 DNA molecules movingfreely in the buffer solution withthe stepwise addition of cetyltri-methylammonium bromide(CTAB). Existence of coil confor-mation of T4 DNA molecules (A),globule conformation (B), andcoexistence of coil state andglobule state (C). Reprinted fromRef. 30, with permission.

10.0 µm

DNA-lipid systems

DNA compaction can occur on thesurface of cationic vesicles

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DNA-surfactant aggregates displaya rich interfacial behavior

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Figure 7. Light microscopy images of single T4 DNA globules adsorbed onto the surface ofpositively charged catanionic vesicles. Arrows indicate single DNA globules. Reprinted fromRef. 38, with permission.

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50-80 Å

Low molecular weight High molecular weight

Phase separation Phase separation

Figure 8. Schematic representation of DNA-cetyltrimethylammonium bromide (CTAB) ad-sorption on silica. For low molecular weight DNA, adsorption is observed for a wide range ofCTAB concentrations. With high molecular weight DNA, precipitation appears to dominateover a very wide range of CTAB concentrations.

DNA-lipid systems

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DNA compaction can be triggered bypH for certain surfactants

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The structure of DNA-surfactantcomplexes is important

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0 5000 2.5 x 1042 x 1041 x 104 1.5 x 104

No surfactant

<2 x 106 M CTAB

250 Å

Figure 9. A, Adsorbed amount (open squares) and adsorbed layer thickness (triangles) as afunction of time. The DNA (700 bp) is added at time 0 (0.06 mg/ml), at t 5000 s cetyltri-methylammonium bromide (CTAB) is added at a concentration of 1.5 x 10-6 M. Then theCTAB concentration is increased stepwise up to t 17,000 s when rinsing is started.Reprinted from Ref. 40, with permission. B, Schematic representation of the system. Withno surfactant added DNA adsorbs slowly onto the surface. With the addition of thesurfactant the adsorbed amount increases but the adsorbed layers compact strongly.

Time (s)

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-4.05.5 6.0 6.5 7.0 7.5

Figure 10. Phase map of the T4 DNA-dodecyldimethyl-amine oxide (DDAO) system at 25�C in 50 mM NaClobtained with fluorescence microscopy at various pHvalues of the surfactant solution (as measured beforemixing with DNA). Coil T4 DNA molecules are repre-sented by crosses, the coexistence of unfolded andcondensed T4 DNA molecules is represented by opencircles, and the compact globular state of all DNA mol-ecules by closed circles. Reprinted from Ref. 33, withpermission.

Figure 11. Multilamellar structures formed in DNA-dodecyldimethylamine oxide (DDAO):dioleoyl-phosphatidylethanolamine (DOPE) mixtures underacidic conditions (pH = 5.5). A, Cryo-TEM image ofvitrified DNA-mixed vesicles complexes in 50 mMNaCl aqueous solutions (scale bar = 90 nm). B,Magnified detail of the multilamellar pattern fromA. C, Fourier transforms of B. D, Precipitated DNA-(DDAO:DOPE) complexes (DNA:DDAO molar ratiois 1:1). Reprinted from Ref. 51, with permission.

0.05 0.1 0.15 0.2 0.25 0.3

q (Å-1)

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DNA compaction can be reversed inmixed surfactant systems

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Figure 12. A, T4 DNA moleculesin the compacted conformationdue to the presence of the cat-ionic surfactant cetyltrimethyl-ammonium bromide (CTAB), insolution. B, For intermediateamounts of the anionic surfac-tant sodium octylsulfate (SOS),we can see a coexistence be-tween the two DNA conforma-tions, i.e., coils and globules. C,With further addition of SOS allmolecules undergo decompac-tion. T = 25�C.

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A polycation compacts DNA in asimilar way as a surfactant aggregate

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L (µm)

Condensed DNA

Coils+condensed DNA

Figure 14. A, Effect of chitosan chain length (or numberof charges) on DNA condensation. A change in distribu-tion of long-axis length of T4 DNA in aqueous solutionsof different chitosan oligomers is observed ([chitosan]:[DNA] charge ratio is equal, 5:1). B, Correlation be-tween the transgene expression of chitosan oligomer/polymer-plasmid DNA complexes and the T4 DNA con-formational state for the same oligomer/polymer for-mulations as visualized by fluorescence microscopy.(W) - Formulations prepared in water (pH 6.1), (B) -formulations prepared in acetate buffer (pH 5.0). UPC =ultrapure polymeric chitosan. Reprinted from Ref. 51,with permission.

Figure 13. Dependence of the conformational behaviorof T4 DNA molecules in aqueous buffer solution atconstant log[DTAB] = -3.5 on the concentration of so-dium dodecylsulfate (N = 12) and sodium octylsulfate(N = 8). Filled circles correspond to the globular DNAconformation, shaded circles to the coexistence of elon-gated coils and compact globules, and open circles tothe coiled conformation state of DNA. T = 25�C. DTAB,dodecyltrimethylammonium bromide.

N = 12

-5 -4 -3 -2 -1

log[SCnS]

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Many aspects remain poorlyunderstood

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Acknowledgments

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References

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