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Issue 3, 2018
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Probing fibronectin conformation on a protein corona layer around nanoparticles

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Protein unfolding induced by nanoparticles (NPs) can lead to exposure of cryptic epitopes that might dictate biological identity and affect NP biological fate (e.g., blood circulation time, biodistribution, and tumor accumulation). Here, we monitor the conformation of fluorescence resonance energy transfer (FRET)-labelled fibronectin (FN) on corona-coated gold NPs. We found that the labelled FN proteins, which directly accessed the gold NP surface, underwent more pronounced conformational changes than those associated with the protein corona via protein–protein interactions. FRET and liquid chromatography–mass spectrometry analyses demonstrated that NP size/concentration, pH change, and the level of surface coverage by the corona can tune the accessibility of labelled FN to the gold NP surface. Although some subsequently adsorbing proteins accessed the NP surface thanks to incomplete surface coverage and protein exchange (the Vroman effect), most outer-layer proteins could not directly bind to the NP surface, blocked by pre-adsorbed corona layers. This finding was also partially confirmed by isothermal titration calorimetry (ITC) analysis. These results suggest the proof-of-concept that outermost-layer proteins with modestly changed conformation rather than unfolded proteins at the gold NP surface effectively create the NPs’ biological identity, which might have important implications on biological fates of gold NPs.

Graphical abstract: Probing fibronectin conformation on a protein corona layer around nanoparticles

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Publication details

The article was received on 19 Sep 2017, accepted on 08 Dec 2017 and first published on 11 Dec 2017

Article type: Paper
DOI: 10.1039/C7NR06970G
Citation: Nanoscale, 2018,10, 1228-1233
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    Probing fibronectin conformation on a protein corona layer around nanoparticles

    M. Raoufi, M. J. Hajipour, S. M. Kamali Shahri, I. Schoen, U. Linn and M. Mahmoudi, Nanoscale, 2018, 10, 1228
    DOI: 10.1039/C7NR06970G

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