Nanoscale Material Size Shapes Distinct Immune Transcriptional States Under Physiological Flow

Abstract Nanoscale materials interact with circulating immune cells, yet how material size and exposure complexity shape transcriptional state organization under physiological flow conditions remains poorly understood. Controlled microfluidic exposure is combined with single-cell RNA sequencing to examine how size-defined polystyrene nanoplastics (PSNPs; 40 nm, 200 nm) and their combination modulate transcriptional programs in primary human peripheral blood mononuclear cells (PBMCs) under dynamic flow conditions. Across immune populations, PSNP exposure induces a conserved translational and RNA-regulatory program, indicating a shared intracellular adaptation framework. Upon this backbone, innate and adaptive immune compartments exhibit distinct organizational principles. Monocytes undergo size-dependent, pathway-coherent state remodeling, whereas B cells and CD4⁺ T cells display distributed, lineage-preserving transcriptional tuning without discrete state transitions. Combined exposure to different particle sizes does not produce additive responses but instead generates integrated transcriptional states in monocytes, revealing non-linear immune adaptation to heterogeneous material cues. These findings demonstrate that nanoscale material size and exposure complexity shape immune transcriptional state architecture under physiological flow and establish a framework for understanding dynamic material–immune interfaces at single-cell resolution.