Insight into the mechanism of antimicrobial conjugated polyelectrolytes: lipid headgroup charge and membrane fluidity effects.

The interactions of antimicrobial cationic conjugated polyelectrolytes (CPEs) with two model membranes, liposomes and lipid monolayers at the air-water interface, have been investigated by fluorescence emission, fluorescence quenching, pressure-area isotherm, and dynamic light scattering measurements. This study continues the evaluation of the antimicrobial mechanism of a cationic poly(phenylene ethynylene) (PPE)-based CPE (polymer 1), which contains a 2,5-thienylene moiety in the repeat unit. To this end, the interactions of polymer 1 with lipids with varying headgroup charge and acyl chain length have been examined. Our results show that the cationic polymer 1 can efficiently associate with and insert into anionic phosphatidylglycerol (PG) membranes. However, polymer 1 does not exhibit any interactions with zwitterionic lipid membranes composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) lipids. Polymer 1's selective affinity toward anionic lipids over zwitterionic lipids makes it an attractive antimicrobial agent with low toxicity. The interactions of polymer 1 with lipid membranes of different fluidity were studied by varying the surface pressure of lipid monolayers and by adjusting the temperature of liposomes. We observe that increasing membrane fluidity enhances both the conformational changes of polymer 1 upon associating with lipid membranes and the extent of polymer 1 insertion into lipid monolayers. We also find that the thickness of the lipid bilayers, modulated by acyl chain length, affects the extent of polymer 1 incorporation into the lipid bilayer.