Rethinking bacterial membrane models in molecular modeling: is the cell wall dispensable in nanomaterial-bacterial membrane interaction?

• The cell wall is significant to the interaction between bacterial membrane and nanomaterials. • The cell wall serves as shield via adsorbing the MoSSe nanosheet. • The membrane without cell wall shows robust perturbation by the MoSSe nanosheet. • The atomic level molecular mechanism has been revealed. Molecular dynamics (MD) simulations offer atomic-level insights into nanomaterial-bacterial membrane interactions, where membrane often lack the cell wall. Therefore, the impact of the cell wall on nanomaterial–membrane interaction modeling remains unclear by far. In this study, we constructed two membrane models: one mimicking a realistic Gram-negative bacterial membrane containing polysaccharides (a major composition of cell wall) in the outer leaflet, and another simplified one lacking polysaccharides. Both models were exposed to a representative nanomaterial, the MoSSe nanosheet, and subjected to extensive MD. Our results show that MoSSe remains stably adsorbed on the polysaccharide layer of the realistic membrane even sustaining a very long simulation time, while it readily inserts into the simplified membrane within a much shorter simulation time. Structural analyses—including membrane thickness, lipid order parameters, and mean square displacement—indicate that MoSSe perturbs the simplified membrane significantly but has minimal effect on the realistic membrane. Dynamic interaction patterns also differ notably between the two models. All these investigations confirm the importance of cell wall on the dynamic interaction by nanomaterials. Interestingly, potential of mean force (PMF) calculations show inconsistencies with unbiased MD simulations, likely due to the limited MD simulation timescales and the multi-atomic-layers of MoSSe.