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bioRxiv · 10.64898/2026.07.02.735952

Clinically derived micro- and nanoplastics uptake drives spatiotemporally confined metabolic stress revealed by bond-selective imaging

Li, J.·Liu, N.·Zhang, D.·Lee, H. J.
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Abstract

Although microplastics and nanoplastics (MP/NP) are pervasive environmental contaminants, our understanding of cellular toxicity remains incomplete, as adverse effects are often attributed to long-term intracellular accumulation, while the spatiotemporal onset of cellular damage remains poorly defined. Here, we employ chemical-bond-selective stimulated Raman scattering (SRS) microscopy and cell models that decouple continuous exposure from intracellular retention to directly visualize clinically derived MP/NP-cell interactions. Cellular stress occurs primarily during MP/NP exposure, accompanied by alterations in lipid droplet (LD) composition. In contrast, following extracellular removal, intracellularly retained MP/NP become largely inert, with recovery of lipid metabolism and cellular functions. Lipidomics identifies arachidonic acid (AA) as a key dysregulated metabolite, and SRS imaging further reveals transient, spatially confined AA enrichment in MP/NP-proximal LDs during uptake. Importantly, phospholipid coating of MP/NP attenuates LD alterations and cytotoxicity while preserving particle internalization, establishing uptake-driven metabolic stress, rather than long-term intracellular retention, as primary source of MP/NP-induced damage.

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Li, J., Liu, N., Zhang, D., Lee, H. J.. 2026-07-07. Clinically derived micro- and nanoplastics uptake drives spatiotemporally confined metabolic stress revealed by bond-selective imaging. https://doi.org/10.64898/2026.07.02.735952

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