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

ABSTRACT 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; O 2 )) 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; O 2 ), ether‐linked phosphatidic acid (PA(O‐34:1)), and hexosylceramide (HexCer(30:1; O 2 )) 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.