High content analysis at single cell level identifies different cellular responses dependent on nanomaterial concentrations.
A mechanistic understanding of nanomaterial (NM) interaction with biological environments is pivotal for the safe transition from basic science to applied nanomedicine. NM exposure results in varying levels of internalized NM in different neighboring cells, due to variances in cell size, cell cycle phase and NM agglomeration. Using high-content analysis, we investigated the cytotoxic effects of fluorescent quantum dots on cultured cells, where all effects were correlated with the concentration of NMs at the single cell level. Upon binning the single cell data into different categories related to NM concentration, this study demonstrates, for the first time, that quantum dots activate both cytoprotective and cytotoxic mechanisms, resulting in a zero net result on the overall cell population, yet with significant effects in cells with higher cellular NM levels. Our results suggest that future NM cytotoxicity studies should correlate NM toxicity with cellular NM numbers on the single cell level, as conflicting mechanisms in particular cell subpopulations are commonly overlooked using classical toxicological methods.
MoSAIC/Biomedical MRI Unit, Faculty of Medicine, KU Leuven, Herestraat 49, B3000 Leuven, Belgium.
Bella B
BB
Manshian
Vlaams Instituut voor Biotechnologie (VIB), Center for the Biology of Disease, Leuven, Belgium.|Center for Human Genetics and Leuven Institute for Neuroscience and Disease (LIND), University of Leuven (KU Leuven), Leuven, Belgium.
Sebastian
S
Munck
Lab of Cell Death and Therapy, Faculty of Medicine, KU Leuven, Herestraat 49, B3000 Leuven, Belgium.
Patrizia
P
Agostinis
MoSAIC/Biomedical MRI Unit, Faculty of Medicine, KU Leuven, Herestraat 49, B3000 Leuven, Belgium.
Uwe
U
Himmelreich
MoSAIC/Biomedical MRI Unit, Faculty of Medicine, KU Leuven, Herestraat 49, B3000 Leuven, Belgium.
Stefaan J
SJ
Soenen
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D005347:Fibroblasts; D059630:Mesenchymal Stem Cells; D051379:Mice; D049329:Nanostructures / Q000633:toxicity; D045663:Quantum Dots; D059010:Single-Cell Analysis / Q000379:methods