Interaction of DNA with likely-charged lipid monolayers: An experimental study

Anionic lipids are increasingly being used in lipoplexes for synthetic gene vectors as an alternative to cationic lipids. This is primarily due to their lower toxicity, which makes them biocompatible and adaptable to be tissue specific. However, anionic lipoplexes require the presence of multivalent cations to promote the electrostatic attraction between DNA and anionic lipid mono- and bilayers. In this work we provide for the first time experimental results of the adsorption of linear DNA onto anionic/zwitterionic lipid monolayers without any addition of cations. This is demonstrated experimentally by means of Langmuir monolayers of DOPE/DOPG (1:1) lipids spread on a water subphase that contains calf thymus DNA. The adsorption of DNA onto anionic/zwitterionic lipid monolayers is discussed in terms of the surface pressure-molecular area isotherms recorded in the absence and in the presence of different electrolytes. Measurements of the surface potential provide additional evidence of the different interaction of DNA anionic/zwitterionic lipid monolayers depending on the presence and nature of electrolyte. These experimental results are further analysed in terms of the overall dipole moment normal to the monolayers providing new insight into the behaviour of anionic lipoplexes and the role of zwitterionic lipids.