Single-Mode Fiber Image Relay Mass Spectrometry Imaging Reveals Lipid Heterogeneity during Drug-Induced Apoptosis

Cellular lipid heterogeneity serves as a critical determinant of cell phenotypes and metabolic states, orchestrating diverse biological processes from signal transduction to stress responses. Thus, high-spatial-resolution mass spectrometry imaging (MSI) is crucial for resolving single-cell lipid heterogeneity. Here, we present a rapidly deployable, easily installed single-mode fiber image relay MSI platform with submicrometer spatial resolution (∼800 nm) at a remote working distance (≥25 mm). With the integrated advantages of plasmonic gold nanoparticles (AuNPs), we successfully visualized numerous lipid distributions in mouse brains and individual HeLa and HepG2 cells. Using this platform, we further performed cell-phenotype-specific lipid profiling and applied it to quantify dose- and time-dependent lipid remodeling during emodin-induced apoptosis in HeLa cells. The results reveal that emodin elicits progressive, network-mediated metabolic reprogramming that, unlike the acute collapse observed under UV irradiation, suppresses structural phospholipids while mobilizing energy reserves. Comparative analyses across cell types and multiple drugs revealed mechanism-dependent lipid fingerprints and pronounced single-cell heterogeneity. In summary, these results establish an accessible route to the MSI shift in lipid metabolism linked with apoptosis at single-cell resolution.