Upon introduction into biological fluids, engineered nanoparticles generally acquire a coating or corona of biomolecules, particularly proteins. Protein association with nanoparticles is commonly discussed in terms of a tightly adsorbed layer with long residence times (“hard” corona) surrounded by a more loosely bound layer susceptible to more rapid exchange with the surrounding solution (“soft” corona). Proteins in hard coronas have been shown to undergo conformational changes; however, the degree to which soft corona proteins undergo conformational changes that persist after desorption from nanoparticles is largely unknown. Given that protein abundance is finely regulated in living cells and that altered protein conformations are closely related to biological responses and even disease, conformational changes induced by interactions of soft corona proteins with nanoparticles must be investigated to better understand potential adverse impact on living organisms. In this study, we examined the extent to which cytosolic proteins undergo persistent conformational changes after transient exposure to nanoparticles, at proteome-wide level. To accomplish this objective, we employed thermal proteome profiling to probe perturbations of protein conformations. We present preliminary results indicating that incubation of cationic gold nanoparticles with cytosolic protein extracts from rainbow trout gill cells resulted in changes of thermal stabilities of specific proteins that are consistent with protein conformation changes. The affinities of cytosolic protein for the biomolecular corona-nanoparticle complex differed as did the degree of conformational change. Our results demonstrate that transient nanoparticle interactions with cellular proteins lead to conformational changes that persist after desorption. Our findings have profound implications for the biological impacts of nanoparticle exposure.

Transient protein interaction with nanoparticle produces persistent conformational changes

256th National Meeting (2018)

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