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Nanotoxicology. 2016 Dec;10(10):1555-1564. Epub 2016 Oct 25.

RNA-binding proteins are a major target of silica nanoparticles in cell extracts.

Author information

1
a I2BC, IBITEC-S, CEA, CNRS, Université Paris-Sud, Université Paris-Saclay , Gif-sur-Yvette , France.
2
b LIONS, NIMBE, CEA, CNRS, Université Paris-Saclay, CEA Saclay , Gif-sur-Yvette , France.
3
c Univ. Grenoble Alpes, CEA, INAC-SyMMES, Laboratoire Lésions des Acides Nucléiques , Grenoble , France , and.
4
d CEA-Marcoule, DRF/IBITEC-S/SPI/Li2D, Laboratory 'Innovative technologies for Detection and Diagnostics', BP 17171 , Bagnols-sur-Cèze , France.

Abstract

Upon contact with biological fluids, nanoparticles (NPs) are readily coated by cellular compounds, particularly proteins, which are determining factors for the localization and toxicity of NPs in the organism. Here, we improved a methodological approach to identify proteins that adsorb on silica NPs with high affinity. Using large-scale proteomics and mixtures of soluble proteins prepared either from yeast cells or from alveolar human cells, we observed that proteins with large unstructured region(s) are more prone to bind on silica NPs. These disordered regions provide flexibility to proteins, a property that promotes their adsorption. The statistical analyses also pointed to a marked overrepresentation of RNA-binding proteins (RBPs) and of translation initiation factors among the adsorbed proteins. We propose that silica surfaces, which are mainly composed of Si-O- and Si-OH groups, mimic ribose-phosphate molecules (rich in -O- and -OH) and trap the proteins able to interact with ribose-phosphate containing molecules. Finally, using an in vitro assay, we showed that the sequestration of translation initiation factors by silica NPs results in an inhibition of the in vitro translational activity. This result demonstrates that characterizing the protein corona of various NPs would be a relevant approach to predict their potential toxicological effects.

KEYWORDS:

Protein corona; RNA binding protein; intrinsically disordered protein; proteomics; silica nanoparticles

PMID:
27705051
DOI:
10.1080/17435390.2016.1244299
[Indexed for MEDLINE]

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