Physical Response of Pseudomonas Aeruginosa Outer Membrane to Signaling Molecule Insertion

Gram-negative bacteria utilize various signaling molecules to increase their chances of survival. Involved in quorum sensing, these small molecules help bacteria with nutrient acquisition, virulence factor production, and inter-cell communication. Moreover, signaling molecules can enhance cells’ ability to resist antibiotics. The Pseudomonas Quinolone Signal (PQS), a prominent signaling molecule for the Pseudomonas aeruginosa bacteria, enables additional protection by facilitating outer membrane vesicles’ formation, which contributes to a defensive barrier for the bacterium. Using an accurate in silico model, this work explores how PQS interaction varies physical properties of P. aeruginosa outer membrane. The model membrane is constructed using all-atom molecular dynamics simulation with an asymmetrical composition, a distinct feature for gram-negative bacteria. The inner leaflet comprises a POPE and POPG phospholipids mixture, while the outer leaflet contains PA14 Lipid A exclusively. PQS spontaneously intercalates into this membrane due to its strong hydrophobicity and specific interactions with Lipid A. We investigate the membrane properties post-intercalation as a function of PQS concentration in the outer leaflet. The structural analysis shows that while PQS does not vary the order parameter of inner leaflet acyl chains, it does enhance the outer leaflet ordering. This enhancement correlates with membrane differential stress, indicating the crowding of the outer leaflet after the PQS intercalation. In addition, we probe the influence of PQS addition on membrane deformability, particularly the effect of PQS concentration on mechanical attributes like compressibility and bending moduli. These insights provide a deeper understanding of PQS’s role and impact on membrane physical properties, contributing valuable information to the field.