Targeting the Weak Spot: Preferential Disruption of Bacterial Poles by Janus Nanoparticles.

The interaction between nanoparticles (NPs) and bacterial cell envelopes is crucial for designing effective antibacterial materials against multi-drug-resistant pathogens. However, the current understanding assumes a uniform bacterial cell wall. This study challenges that assumption by investigating how bacterial cell wall curvature impacts antibacterial NP action. Focusing on Janus NPs, which feature segregated hydrophobic and polycationic ligands and previously demonstrated high efficacy against diverse bacteria, we found that these NPs preferentially target and disrupt bacterial poles. Experimental and computational approaches reveal that curvature at poles induces conformational changes in lipopolysaccharide (LPS) polymers on the outer membrane, exposing underlying lipids for NP-mediated disruption. We establish that curvature-induced targeting by Janus NPs depends on the outer membrane composition and is most pronounced at physiologically relevant LPS densities. This work demonstrates that high-curvature regions of bacterial cell walls are "weak spots" for Janus NPs, thereby aiding the development of more effective targeted therapies.