Spatial Detection of Microsphere Polystyrene Plastics and Molecular Remodeling within a Full‐Body Mouse with MALDI Trapped Ion Mobility Mass Spectrometry Imaging

Polystyrene (PS), a widely used synthetic polymer, breaks into micro- and nanoscale particles that can enter the body and accumulate in tissues. Conventional methods provide bulk chemical information, but lack spatial and metabolic context. Here, we use matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) with trapped ion mobility spectrometry (TIMS) to localize PS across whole-body murine sections and individual organs, allowing differentiation of PS chain lengths and associated metabolic shifts. Oral PS exposure produced clear organ-specific lipid remodeling. In the stomach, increases in phosphatidylcholine (PC(30:2)), phosphatidic acid (PA(36:1)), and sphingomyelin (SM(34:1; O2)) suggest epithelial stress and barrier disruption. In the liver, PC(32:1) decreased, and higher PC(30:2) and PA(36:2) indicate impaired lipid export alongside compensatory adjustments to maintain membrane stability, with potential effects on systemic lipid balance. In the heart, reductions in SM(32:1; O2), ether-linked phosphatidic acid (PA(O-34:1)), and hexosylceramide (HexCer(30:1; O2)) reflect disrupted sphingolipid and ether-linked lipid species metabolism and altered lipid transport. Together, these findings reveal dynamic, tissue-specific lipid responses to PS exposure. This study shows that MALDI TIMS MSI provides high-resolution, label-free mapping of PS and its metabolic footprint and can be extended to other low-abundance synthetic compounds.