Single cell mechanics, derived from atomic force microscopy-based technology in conjunction with in vivo exposure, provides a new and effective readout for monitoring nanoparticle-cell interactions, as such nanocytotoxicity. Macrophages represent a major defense mechanism by which inhaled particles are removed from the respiratory tract. Cellular mechanics has previously been shown to be a sensitive indicator in human aortic endothelial cells’ disruption upon in vitro exposure to nanomaterials. This study extends the single cell mechanics approach to probe the cytotoxicity of nanomaterials upon in vivo exposure. Materials included 20 and 110 nm silver nanoparticles (AgNPs), which were pre-dispersed in designated solvents. Instillation by rats was completed at a dosage of 0.5 mg AgNPs/kg body weight, and then the bronchoalveolar lavage was collected one day later to harvest living macrophage cells. The intracellular AgNPs exhibit a high degree of variation among AMs due to intake and intracellular physio-chemical status of AgNPs, and as such, subsequent single cell mechanics are measured from representative cells from each subpopulation. These measurements indicate a multitude of effects, ranging from reduction of membrane fluidity, increase of membrane elastic compliance, ion flux dysfunction, to cytoskeleton damage and cell death. The impact depends on the aggregation and solubility of AgNPs. This investigation reveals that single cell based studies are a necessary and valuable tool to probe in vivo pulmonary nanotoxicity. The advantages and limitations of this single cell based approach in the context of nanotoxicity are also discussed.

Probing interactions between nanoparticles and cellular membrane via single cell mechanics

249th National Meeting (2015)

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