Figure 5.
Proposed Mechanism of Action for Membrane Disruptive Effects of Cationic Lipids
In isolation, cationic lipids and anionic lipids present in the endosome (such as lyso-bis phosphatidic acid) adopt a cylindrical molecular shape, which is compatible with packing in a bilayer configuration. However, when cationic and anionic lipids are mixed together, they combine to form ion pairs where the cross-sectional area of the combined head group is less than that of the sum of individual head group areas in isolation. The ion pair therefore adopts a molecular “cone” shape, which promotes the formation of inverted, non-bilayer phases such as the hexagonal HII phase illustrated. Inverted phases do not support bilayer structure and are associated with membrane fusion and membrane disruption. Adapted from Semple et al.16