Characterization of the cationic DiC(14)-amidine bilayer by mixed DMPC/DiC(14)-amidine molecular dynamics simulations...

DiC(14)-amidine (amidine) is a nonphysiological, cationic lipid that forms stable liposomes under physiological pH and temperature. Cationic lipids have been proposed as delivery vector for DNA, proteins, and drugs. Furthermore, amidine carries at present a particular interest due to its immunomodulatory properties. (1-3) Molecular dynamics simulations reveal a remarkable fluidity in the hydrophobic bilayer core, with a tendency for strong surface curvature, in agreement with the relatively small size of experimentally formed liposomes. The amidine bilayer shows an interdigitated, nonlamellar bilayer phase, with a bilayer thickness of only 2.7 nm and an average area per lipid of 0.83 nm(2). A cluster analysis of the individual lipid structures shows a thermally accessible population of V-shaped lipids, indicative of fusion capabilities with the plasma membrane. Fusion experiments confirm this hypothesis. The results are compared to the zwitterionic DMPC (dimyristoylphosphocholine), which also carries two saturated C(14) tails.