Gemini vs. wild-type bacterial lipid monolayers: Effect of surfactant molecular architecture

As the first line of defence, the outer leaflet of the Gram-negative bacteria outer membrane is almost entirely comprised of lipopolysaccharides (LPS smooth). Its polysaccharide O-antigens form a protective polymer brush layer, and the Lipid A moieties are bridged by divalent cations for enhanced leaflet rigidity. Gemini surfactants (two heads and two tails) are conjectured to be particularly effective in breaching this bacterial defensive cell coat, compared to monomeric analogues. For octenidine (OCT), a Gemini surfactant frequently used as a clinical antiseptic, its small size is thought to enable permeation through the O-antigen brush, and its 4-aminopyridinium headgroup can then bind to the anionic Lipid A phosphates through a combination of electrostatic, H-bonding and π-π interactions. Understanding interactions underpinned by OCT’s molecular architecture is vital to future rational design of more sustainable antimicrobial Gemini surfactants for industrial formulation. We propose to use NR to investigate the nanostructural changes in LPS monolayers as a result of interactions with three OCT-analogues, with same skeletal structure but different headgroups. This will allow a correlation between the membrane thickness, membrane elasticity, molecular packing, and the surfactant architecture, informing on the optimal Gemini design against Gram-negative bacteria