Label‐Free Characterization of Lipid Interfaces Using Plasmonic Gold Nanorods as Optically Active Nanosensors

Abstract Lipid membrane research bridges biology, chemistry, physics, and medicine, offering fundamental insights into molecular life and enabling advances in technology and healthcare. However, traditional analytical methods often introduce nanoscale artifacts, limiting their reliability. Here, single‐nanoparticle plasmon spectroscopy is applied as a label‐free approach to characterize lipid interfaces, with a particular focus on detecting membrane phase transitions. Using gold nanorods as optically active nanosensors, a direct correlation between surface pressure and lipid packing density in 1,2‐dipalmitoyl‐ sn ‐glycero‐3‐phosphocholine monolayers are established, serving as a proof of concept. This relationship allows precise determination of the local refractive index across different interfacial regions. This technique is further applied to monitor the thermotropic phase transition in single lipid bilayers, obtaining results that closely align with fluorescence lifetime measurements. The method provides a simple yet powerful tool for label‐free, high‐resolution analysis of the organization and dynamics of lipid interfaces. Its accessibility and adaptability make it suitable for widespread use in biochemistry and biophysics, and nanomedicine laboratories.