Liquid crystal–aqueous interface renders selective detection of distinct mycobacterial cell envelope responses

Antibiotic-resistant latent tuberculosis mandates sensitive, label-free screening platforms that permit the detection of changes in bacterial membranes as a potential therapeutic target. Growth stage-induced alterations in the mycobacterial lipidome, which underlie drug tolerance, further intensify this goal. In this work, liquid crystal (LC)-based detection captured the selective, spatiotemporal modulation of lipid membranes induced by bacterial dormancy. The LC-aqueous interface effectively differentiated responses across the bacterial cell envelope layers. Next, subtle changes in mycobacterial membranes were detected upon interaction with specific antimicrobial peptides (AMPs) at various growth stages. This showcased the potential of the LC-aqueous interface as a label-free membrane screening diagnostic tool. Collectively, the LC-aqueous interface detected membrane order across envelope layers, dormancy-induced lipidome changes, and mycobacterial membrane disruption by AMPs. The distinct behaviour of the LC-aqueous interface in detecting alterations in lipid membranes during different infection stages could be developed in the future to diagnose latent/active pathogens in tuberculosis or other infectious diseases.