Knifing Action of WS ₂ Nanosheets Toward the Inner Membrane of <i>Escherichia coli</i> Compared to Its Mild and Conditional Detrimental Effect on the Bacterial Membrane of <i>S. aureus</i>

The global rise in mortality rates due to drug-resistant infections necessitates the development of medicinal alternatives, with membrane-targeting antibacterial nanomaterials representing a promising strategy due to their inherently low propensity for resistance development. Notably, two-dimensional transition-metal dichalcogenides (TMDs), such as tungsten disulfide (WS2), have emerged as promising broad-spectrum, membrane-mediated antibacterial agents with favorable biocompatibility. Herein, we investigate the antibacterial mode of action of WS2 nanosheets against two popular pathogenic bacterial strains: Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) using atomistic molecular dynamics simulations. The study reveals the spontaneous permeation of freely dispersed WS2 sheet(s) into the E. coli cytoplasmic model membrane at 310 K, while the sheets are weakly adsorbed on the S. aureus membrane surface under the same conditions, highlighting the influence of the lipid composition of the bacterial membrane on the antibacterial mechanistic pathway. However, when the WS2 sheet is subjected to orientational restraint with vertical sheet alignment with respect to the bilayer normal, the WS2 nanosheet is found to pave its way into the hydrophobic core of the S. aureus membrane, facilitated by the edge approach. Additionally, increasing the thermal energy results in the spontaneous insertion of the unrestrained WS2 nanosheet into the S. aureus membrane, regardless of the initial sheet orientation.