Light-Triggered Mechanotherapy of Membrane-Mimicking Conjugated Electrolytes Potentiates Antibacterial Efficacy

Abstract

The rise of multidrug-resistant (MDR) pathogens has created an urgent need for antibacterial strategies that operate beyond conventional biochemical targets. Here, a light-triggered molecular mechanotherapeutic antibacterial platform based on membrane-mimicking conjugated electrolytes (MMCEs) is reported. Owing to their membrane-compatible architecture, MMCEs can spontaneously intercalate into lipid bilayers while remaining relatively non-disruptive in the dark. To enhance photoinduced mechanical activity, ZBT was developed from the classical BT scaffold by replacing the stilbene-like wing with a biphenyl unit, thereby increasing steric hindrance and molecular torsion. Computational analysis indicated that this structural modification markedly amplified conformational twisting. As a result, ZBT exhibited substantially improved antibacterial performance. Notably, although ZBT generates slightly fewer light-induced reactive oxygen species than BT, its antibacterial activity against MRSA is approximately twice as high, indicating that enhanced light-triggered physical membrane disruption significantly boosts ZBT’s antimicrobial performance. In vitro, ZBT effectively suppressed MRSA biofilm formation and displayed potent photoactivated antibacterial activity. In a murine skin wound infection model, ZBT combined with light achieved efficient bacterial clearance while maintaining excellent biocompatibility. These findings establish MMCE-based mechanotherapy as a promising strategy against drug-resistant bacteria and, more importantly, reveal a molecular design principle in which increasing backbone torsion enhances photoresponsive physical killing.