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

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-MoS2 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-MoS2) selectively kills Gram-negative bacteria, whereas the cis form (cis-Azo-MoS2), under UV light, exhibits antibacterial activity against Gram-positive strains. The mechanistic investigation indicates that the cis-Azo-MoS2 exhibits higher affinity towards the membrane of Gram-positive bacteria compared to trans-Azo-MoS2. In case of Gram-negative bacteria, trans-Azo-MoS2 internalizes more efficiently than cis-Azo-MoS2 and generates intracellular ROS to kill the bacteria. While the trans-Azo-MoS2 exhibits strong electrostatic interactions and internalizes faster into Gram-negative bacterial cells, cis-Azo-MoS2 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 mu g/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. We present a photoswitchable bio-interface through ligand functionalization on #2D-MoS2, achieving differential-interactions-based #Gram-selective antibacterial activity that enables effective wound healing applications. @MrinmoyGroup @funbiomats @iiscbangaloreimage