Binding of DNA to zwitterionic lipid layers mediated by divalent cations. 2009

Demmelash H Mengistu, and Klemen Bohinc, and Sylvio May
Department of Physics, North Dakota State University, Fargo, North Dakota 58108-6050, USA.

Divalent cations, i.e., calcium, magnesium, and others, are able to enhance the ability of DNA to interact with membranes that are composed of zwitterionic lipids such as phosphatidylcholine. The resulting condensed complexes offer potential applications as nontoxic gene delivery vehicles. The present study suggests a generic theoretical model to describe the energetics and structural features of a zwitterionic lipid-DNA complex in the presence of divalent cations. Specifically, we consider the adsorption of a single molecule of double-stranded DNA onto a planar zwitterionic lipid layer. Our theoretical model is based on the continuum Poisson-Boltzmann formalisms, which we modified so as to account for the two opposite charges and orientational freedom of the zwitterionic lipid headgroups. We find a substantially more favorable adsorption free energy of the DNA if divalent cations are present. In addition, our model predicts the divalent cations to preferentially interact with the phosphate groups of the zwitterionic lipids, given these lipids are located in close vicinity to the DNA. This is accompanied by a small but notable reorientation of the zwitterionic headgroups toward the DNA. We demonstrate that the binding of DNA onto a zwitterionic lipid layer is not driven by the release of counterions. Instead, the binding leads to a partial redistribution of the divalent cations, from the phosphate groups of the DNA (prior to the binding) to the phosphate groups of the zwitterionic lipids (after the binding). Our results thus suggest a general physical mechanism underlying complex formation between DNA and zwitterionic lipids in terms of mean-field electrostatics, i.e., neither involving correlations nor specific interactions of the divalent cations.

UI MeSH Term Description Entries
D008051 Lipid Bilayers Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes. Bilayers, Lipid,Bilayer, Lipid,Lipid Bilayer
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D010713 Phosphatidylcholines Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety. Choline Phosphoglycerides,Choline Glycerophospholipids,Phosphatidyl Choline,Phosphatidyl Cholines,Phosphatidylcholine,Choline, Phosphatidyl,Cholines, Phosphatidyl,Glycerophospholipids, Choline,Phosphoglycerides, Choline
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D002413 Cations, Divalent Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis. Divalent Cations
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA

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