Disentangling Gill Cellular and Molecular Responses to Microplastics from Associated Chemicals

Micro and nanoplastics (MNPs) have become defining environmental contaminants of the Anthropocene, functioning not only as persistent physical pollutants but also as dynamic vectors for tens of thousands of synthetic and natural chemicals in aquatic ecosystems. These small plastic particles, typically less than 5mm in size, readily adsorb and transport additives and pollutants such as plasticizers, phthalates, metals, pesticides, and persistent organic pollutants, creating complex particle–chemical mixtures that threaten aquatic organisms, food safety, and ecosystem stability. Despite their ubiquity, our mechanistic understanding of how such mixtures become bioavailable, how aquatic species sense and internalize them, and how chemical and particle stressors interact at the cellular level remains critically limited, representing a major frontier in environmental toxicology and ecological risk assessment. This project aims to disentangle particle mediated and chemical specific effects of MNPs by integrating environmentally realistic exposure experiments with state of the art cellular and molecular technologies. Using two evolutionarily distant but functionally analogous “sensory gill systems”—the marine oyster Crassostrea hongkongensis and the freshwater zebrafish Danio rerio—we will investigate how MNPs and their associated chemicals of concern (COCs) are taken up, transformed, and sensed at molecular and cellular scales. Building upon our recently established single cell transcriptomic atlases for oyster and fish gills, the study introduces a mechanistic “cradle to cell” framework to examine interactions between particulate and chemical stressors across biological complexity. Task1 will quantify the bioavailability and bioaccessibility of representative MNP–COC pairs under environmentally relevant conditions to derive kinetic parameters and exposure models. Task2 will map MNP uptake and chemical specific transcriptional responses in oyster gills using single cell RNA sequencing, supported by histopathology, oxidative stress biomarkers, and functional validation assays. Task3 will extend these analyses to zebrafish gills to identify conserved and cell type specific pathways, including copper induced redox switching under combined exposures. Collectively, these studies will reveal cellular processes that distinguish mechanical from chemical toxicity, identify molecular biomarkers of MNP and COC exposure, and deliver predictive understanding of mixture effects in aquatic systems. Overall, this project will identify differential responses of gill sensors to specific MNPs and chemicals at the cellular and molecular levels and contribute to safer plastic design, improved environmental monitoring, and evidence based risk assessment essential for protecting aquatic and human health in rapidly changing coastal ecosystems.