A systems biology approach to understand temporal evolution of silver nanoparticle toxicity.

Silver nanoparticles (AgNPs) are widely used in industrial and biomedical applications, however, their toxicity mechanisms at the molecular level are not completely understood. To address this gap, we investigate the temporal dynamics of gene expression in human lung epithelial cells exposed to AgNPs, integrating transcriptomic analysis, gene ontology (GO) enrichment, protein-protein interaction (PPI) networks, and dynamic simulations. GO analysis highlights early activation of ribosomal biogenesis and stress pathways, transitioning DNA repair and cell cycle regulation at later stages. PPI networks identify ribosomal proteins and DNA damage regulators as key hub genes. Dynamic simulations modeled gene expression changes over 48 hours, uncovering sequential activation of stress response genes, followed by DNA repair attempts and apoptotic signaling as cellular damage persisted. Through modeling the interplay between molecular responses and cell viability, the simulations provided a predictive temporal framework for advancing nanotoxicology research, providing insights into AgNPs-induced molecular disturbances, contributing to safety assessments.