Atomistic modeling of lysophospholipids from the Campylobacter jejuni lipidome

Lysophospholipids are an important class of lipids in both prokaryotic and eukaryotic organisms. These lipids typically constitute a very small proportion (<1%) of the bacterial lipidome but can constitute 20%-45% of the Campylobacter jejuni lipidome under stress conditions. It is thus of importance to include these lipids in model C. jejuni membrane simulations for an accurate representation of the lipidic complexity of these systems. Here, we present atomistic models for four lysophospholipids from the C. jejuni lipidome, each derived from existing phospholipid models. Herein, we use molecular dynamics simulations to evaluate the ability of these models to reproduce the expected micellar, hexagonal, and lamellar phases at varying levels of hydration. Mixtures of phospholipids and lysophospholipids emulating the C. jejuni lipidome under ideal growth conditions were found to self-assemble into bilayers in solution. The properties of these mixed bilayers were compared with those containing only phospholipids: the presence of the selected lysophospholipids causes a subtle thinning of the bilayer and a reduction in area per lipid, but no significant change in lipid diffusion. We further test the mixed bilayer model running simulations in which a native inner membrane protein is embedded within the bilayer. Finally, we show that lysophospholipids facilitate the formation of pores in the membrane, with lysophospholipid-containing bilayers more susceptible to electroporation than those containing only phospholipids.