Gold nanoparticles cellular toxicity and recovery: effect of size, concentration and exposure time

Gold nanoparticles (AuNPs) are used in many applications; however, their interactions with cells and potential health risk(s) are not fully known. In this manuscript, we describe the interactions of AuNPs with human dermal fibroblasts and show that they can penetrate the plasma membrane and accumulate in large vacuoles. We also demonstrate that the uptake of the AuNPs is a function of time, their size and concentration. Specifically, we demonstrate that 45 nm AuNPs penetrate cells via clathrin-mediated endocytosis, while the smaller 13 nm enter mostly via phagocytosis. Furthermore, we provide evidence of cytoskeleton filament disruption as a result of AuNPs exposure and reconstitution during recovery (following AuNP removal), despite no changes in actin or beta-tubulin protein levels. In contrast, the expression of the extracellular matrix (ECM) proteins, collagen and fibronectin, was diminished in the cells exposed to AuNPs. We also examined the proliferation rates of cells exposed to AuNPs and show that its diminution is a function of apoptosis and speculate that apoptosis results from the number of vacuoles present in the cells, which is probably the main factor that disrupts the cytoskeleton causing cell area contraction and decreases in motility. Lastly, we also present data that indicates that AuNPs' damage to cells is not permanent and that the cells can completely recover as a function of AuNPs' size, concentration and exposure time. Taken together, our data suggest that AuNPs exert detrimental effects on cell function that could reverse following AuNPs removal.