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Nanoparticles can wrap epithelial cell membranes and relocate them across the epithelial cell layer Iztok Urban#i#, Maja Garvas, Bostjan Kokot, Hana Majaron, Polona Umek, Hilary Cassidy, Miha Skarabot, Falk Schneider, Silvia Galiani, Zoran Arsov, Tilen Koklic, David Matallanas, Miran #eh, Igor Musevic, Christian Eggeling, and Janez Štrancar Nano Lett., Just Accepted Manuscript • Publication Date (Web): 24 Jul 2018 Downloaded from http://pubs.acs.org on July 24, 2018
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Nanoparticles can wrap epithelial cell membranes and relocate them across the epithelial cell layer Iztok Urbančič1,2, Maja Garvas1,3, Boštjan Kokot1, Hana Majaron1, Polona Umek1,4, Hilary Cassidy5, Miha Škarabot1, Falk Schneider2, Silvia Galiani2, Zoran Arsov1,4, Tilen Koklic1,4, David Matallanas5,6, Miran Čeh1, Igor Muševič1,7, Christian Eggeling2,8,9, Janez Štrancar1,4*. 1
“Jožef Stefan” Institute, Jamova cesta 39, SI-1000 Ljubljana, Slovenia
2
Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK
3
Jožef Stefan International postgraduate school, Jamova cesta 39, SI-1000 Ljubljana, Slovenia
4
Center of excellence NAMASTE, Jamova cesta 39, SI-1000 Ljubljana, Slovenia
5
Systems Biology Ireland, University College Dublin, Dublin, Ireland
6
School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
7
Faculty of Mathematics and Physics, University of Ljubljana, Jadranska 19, SI-1000 Ljubljana, Slovenia
8
Institute of Applied Optics, Friedrich-Schiller University, Jena, Germany
9
Leibniz Institute of Photonic Technology (IPHT), Jena, Germany.
ABSTRACT: Although the link between the inhalation of nanoparticles and cardiovascular disease is well established, the causal pathway between nanoparticle exposure and increased activity of blood coagulation factors remains unexplained. To initiate coagulation tissue factor bearing epithelial cell membranes should be exposed to blood, on the other side of the less than a micrometre thin air-blood barrier. For the inhaled nanoparticles to promote coagulation, they need to bind lung epithelial-cell membrane parts and relocate them into the blood. To assess this hypothesis, we use advanced microscopy and spectroscopy techniques to show that the nanoparticles wrap themselves with epithelial-cell membranes, leading to the membrane’s disruption. The membrane-wrapped nanoparticles are then observed to freely diffuse across the damaged epithelial cell layer relocating epithelial cell membrane parts over the epithelial layer. Proteomic analysis of the protein content in the nanoparticles wraps/corona finally reveals the presence of the coagulation-initiating factors, supporting the proposed causal link between the inhalation of nanoparticles and cardiovascular disease.
Nanoparticles (NPs) are small (
