Structure, stability, and thermodynamics of lamellar DNA-lipid complexes

Daniel Harries, Sylvio May, William M. Gelbart, Avinoam Ben-Shaul*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

223 Scopus citations

Abstract

We develop a statistical thermodynamic model for the phase evolution of DNA-cationic lipid complexes in aqueous solution, as a function of the ratios of charged to neutral lipid and charged lipid to DNA. The complexes consist of parallel strands of DNA intercalated in the water layers of lamellar stacks of mixed lipid bilayers, as determined by recent synchrotron x-ray measurements. Elastic deformations of the DNA and the lipid bilayers are neglected, but DNA-induced spatial inhomogeneities in the bilayer charge densities are included. The relevant nonlinear Poisson-Boltzmann equation is solved numerically, including self-consistent treatment of the boundary conditions at the polarized membrane surfaces. For a wide range of lipid compositions, the phase evolution is characterized by three regions of lipid to DNA charge ratio, p: 1) for low p, the complexes coexist with excess DNA, and the DNA-DNA spacing in the complex, d, is constant; 2) for intermediate p, including the isoelectric point p = 1, all of the lipid and DNA in solution is incorporated into the complex, whose inter-DNA distance d increases linearly with p; and 3) for high p, the complexes coexist with excess liposomes (whose lipid composition is different from that in the complex), and their spacing d is nearly, but not completely, independent of p. These results can be understood in terms of a simple charging model that reflects the competition between counterion entropy and inter-DNA (p < 1) and interbilayer (p > 1) repulsions. Finally, our approach and conclusions are compared with theoretical work by others, and with relevant experiments.

Original languageAmerican English
Pages (from-to)159-173
Number of pages15
JournalBiophysical Journal
Volume75
Issue number1
DOIs
StatePublished - Jul 1998

Bibliographical note

Funding Information:
The financial support of the Israel Science Foundation (AB-S grant 8003/97), the U.S.-Israel Binational Science Foundation (AB-S and WMG, grant 94/130), and the National Science Foundation (WMG, grant NSF-DMR-9708646) is gratefully acknowledged. SM thanks the Minerva Stiftung for a postdoctoral fellowship. The Fritz Haber research center is supported by the Minerva Foundation, Munich, Germany.

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