Meso-scale computer modeling of lipid-DNA complexes for gene therapy

Abstract

We report on a molecular simulation method which captures the self-assembly of cationic lipid-DNA (CL-DNA) gene delivery complexes. Computational efficiency required for large length- and time-scale simulations is achieved through a coarse-grained representation of the intra-molecular details, and via inter-molecular potentials, which effectively mimic the hydrophobic effect {\em without} explicit solvent. In addition to showing spontaneous self-assembly of complexes, the broad utility of the model is illustrated by demonstrating excellent agreement with X-ray diffraction experimental data for the dependence of the spacing between DNA chains on the concentration of CLs. At high concentrations, the large electrostatic pressure induce the formation of pores in the membranes through which the DNA molecules may escape the complex. We relate this observation to the origin of recently observed enhanced transfection efficiency of lamellar CL-DNA complexes at high charge densities.

4 pages, 3 figures -- submitted for publication August 1, 2005

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Cited by in corpus (8)

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• Critical adsorption of polyelectrolytes onto charged Janus nanospheres
• Transitions between distinct compaction regimes in complexes of multivalent cationic lipids and DNA
• Computational and Analytical Modeling of Cationic Lipid-DNA Complexes
• Mode excitation Monte Carlo simulations of mesoscopically large membranes
• Simple, self-assembling, single-site model amphiphile for water-free simulation of lyotropic phases
• Orientational transition and complexation of DNA with anionic membranes: weak and intermediate electrostatic coupling