Nanoscale Material Size Shapes Distinct Immune Transcriptional States Under Physiological Flow
Nanoplastics interact continuously with circulating immune cells, yet how particle size and exposure complexity shape immune transcriptional organization under physiological flow conditions remains poorly understood. Here, controlled microfluidic exposure was combined with single-cell RNA sequencing to investigate the effects of size-defined polystyrene nanoplastics (PSNPs; 40 nm, 200 nm, and 40 + 200 nm) on primary human peripheral blood mononuclear cells (PBMCs) under dynamic flow conditions. Across immune populations, PSNP exposure induced a conserved ribosome-associated and RNA-regulatory transcriptional program, indicating a shared intracellular adaptive response. Monocytes displayed the strongest transcriptional remodeling, characterized by coordinated modulation of ribosome-associated, metabolic, and inflammatory signaling pathways in a size-dependent manner. Exposure to 40 nm PSNPs negatively enriched (suppressed) mitochondrial metabolic pathways, whereas 200 nm PSNPs enriched inflammatory signaling programs. Combined exposure induced concurrent metabolic and inflammatory pathway engagement without evidence of major immune topology disruption or discrete inflammatory state transitions. In contrast, adaptive immune cells exhibited comparatively modest and lineage-preserving transcriptional modulation. Together, these findings demonstrate that nanoplastic size and exposure complexity shape coordinated immunometabolic adaptation in human immune cells under physiologically relevant flow conditions and establish a framework for studying dynamic material-immune interactions at single-cell resolution.