Photo‐Controlled Gating of Selective Bacterial Membrane Interaction and Enhanced Antibacterial Activity for Wound Healing

Abstract Reversible biointerfaces are essential for on‐demand molecular recognition to regulate stimuli‐responsive bioactivity such as specific interactions with cell membranes. The reversibility on a single platform allows the smart material to kill pathogens or attach/detach cells. Herein, we introduce a 2D‐MoS 2 functionalized with cationic azobenzene that interacts selectively with either Gram‐positive or Gram‐negative bacteria in a light‐gated fashion. The trans conformation ( trans ‐Azo‐MoS 2 ) selectively kills Gram‐negative bacteria, whereas the cis form ( cis ‐Azo‐MoS 2 ), under UV light, exhibits antibacterial activity against Gram‐positive strains. The mechanistic investigation indicates that the cis ‐Azo‐MoS 2 exhibits higher affinity towards the membrane of Gram‐positive bacteria compared to trans ‐Azo‐MoS 2 . In case of Gram‐negative bacteria, trans ‐Azo‐MoS 2 internalizes more efficiently than cis ‐Azo‐MoS 2 and generates intracellular ROS to kill the bacteria. While the trans ‐Azo‐MoS 2 exhibits strong electrostatic interactions and internalizes faster into Gram‐negative bacterial cells, cis ‐Azo‐MoS 2 primarily interacts with Gram‐positive bacteria through hydrophobic and H‐bonding interactions. The difference in molecular mechanism leads to photo‐controlled Gram‐selectivity and enhanced antibacterial activity. We found strain‐specific and high bactericidal activity (minimal bactericidal concentration, 0.65 μg/ml) with low cytotoxicity, which we extended to wound healing applications. This methodology provides a single platform for efficiently switching between conformers to reversibly control the strain‐selective bactericidal activity regulated by light.