Role of O-Antigen in Response to Mechanical Stress of the E. coli Outer Membrane: Insights from Coarse-Grained MD Simulations.

Lipopolysaccharide (LPS) is an important component of the outer membrane of Gram-negative bacteria, contributing to the structural integrity of the bacterial cell wall and conferring resistance to chemical attack. The rough variant of LPS contains a conserved lipid A domain and a complete core saccharide section, whereas the smooth variant additionally contains a terminal O-antigen chain. In the following, smooth LPS lipids are simulated in multicomponent membrane models using coarse-grained molecular dynamics. The simulations reveal that the lipid environment of smooth LPS lipids affects the orientation and clustering of their O-antigen chains. When the outer membrane leaflets contain smooth LPS lipids alone, the O-antigen chains are packed tightly, leading to strong cohesive intermolecular interactions. When the outer leaflets incorporate interstitial phospholipids and rough LPS variants, the O-antigen chains are tilted and less tightly bound. The different packing of terminal O-antigen chains affects lipid mobility and the mechanical strength of the Gram-negative membrane models. Gram-negative membranes with outer leaflets of smooth LPS alone can withstand surface tensions (150 mN m) that cause the membrane models with rough LPS lipids and comparable phospholipid bilayers to rupture much more readily.