Nanometer-Precision Tracking of Adipocyte Dynamics via Single Lipid Droplet Whispering-Gallery Optical Resonances

Biophotonics─and more recently, biointegrated photonics─offer transformative tools for probing cellular processes with unprecedented precision. Among these, whispering-gallery-mode (WGM) resonators (optical microcavities formed in spherical structures) have emerged as powerful biosensors and intracellular barcodes. Lipid droplets (LDs), with their high refractive index and intrinsic spherical geometry, are ideal candidates for supporting intracellular lasing. Although lasing in LDs has been previously demonstrated, it has not yet been harnessed to study live-cell biology. Here, we report the first use of WGM resonances in LDs of live primary adipocytes, employing a continuous-wave (CW) laser at powers below the biological damage threshold. By measuring these resonances, we achieved nanometer-scale precision in size estimation, enabling real-time observation of rapid LD dynamics and deformations on the minute scale─far beyond the spatiotemporal resolution of conventional microscopy. We systematically characterized this photonic sensing approach, demonstrating its ability to resolve adipocyte heterogeneity, monitor lipolytic responses to forskolin and isoproterenol, and detect early signs of cell viability loss─well before conventional assays. This proof-of-concept establishes intracellular LD WGM resonances as a robust platform for investigating live single-cell metabolism. The technique enables rapid, cost-effective assessment of adipocyte function, reveals cell-to-cell variability obscured by bulk assays, and lays the foundation for high-throughput analysis of metabolism- and obesity-related diseases at both the cellular and tissue levels.