Interaction of Ionenes with Lipid Membrane: Unusual Impact of Charge Density

Synthetic water-soluble polymers are increasingly used for gene delivery, stabilization, and delivery of proteins, and as prospective antimicrobial and antiviral agents. Therefore, study of their interaction with lipid membranes is of special importance. Herein, we studied interaction of aliphatic cationic ionenes (recently tested for gene delivery efficiency) differed in the length of spacer between charged groups (and therefore in charge density) with anionic lipid membrane. A range of approaches such as measurement of particle size and electrophoretic mobility, liposome integrity, ATR-FTIR spectroscopy, isothermal titration calorimetry as well as atomistic molecular modeling was used. Ionene with a spacer of 10 methylene groups has been shown to be incorporated into membrane and interact with its inner hydrophobic part in contrast to ionenes with shorter spacer, which interacted only with outer polar head groups of lipids staying at the water-membrane interface. It affects membrane integrity and results in a different behavior of the polymer-liposome complexes. These findings are relevant for potential biomedical application of ionenes, including creation of composite polymer-liposome systems for drug delivery.