Molecular simulation analysis of structural variations in lipoplexes

Physics – Condensed Matter – Soft Condensed Matter

Scientific paper

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Accepted for publication in "Soft Matter"

Scientific paper

We use a coarse-grained molecular model to study the self-assembly process of complexes of cationic and neutral lipids with DNA molecules ("lipoplexes") - a promising nonviral carrier of DNA for gene therapy. We identify the resulting structures through direct visualization of the molecular arrangements and through calculations of the corresponding scattering plots. The latter approach provides a means for comparison with published data from X-ray scattering experiments. Consistent with experimental results, we find that upon increasing the stiffness of the lipid material, the system tends to form lamellar structures. Two characteristic distances can be extracted from the scattering plots of lamellar complexes - the lamellar (interlayer) spacing and the DNA-spacing within each layer. We find a remarkable agreement between the computed values of these two quantities and the experimental data [J. O. R\"{a}dler, I. Koltover, T. Salditt and C. R. Safinya, Science Vol. 275, 810 (1997)] over the entire range of mole fractions of charged lipids (CLs) studied experimentally. A visual inspection of the simulated systems reveals that, for very high fractions of CLs, disordered structures consisting of DNA molecules bound to small membrane fragments are spontaneously formed. The diffraction plots of these non-lamellar disordered complexes appear very similar to that of the lamellar structure, which makes the interpretation of the X-ray data ambiguous. The loss of lamellar order may be the origin of the observed increase in the efficiency of lipoplexes as gene delivery vectors at high charge densities.

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