Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization
While the interaction between 2D materials and cells is of key importance to the development of nanomedicines and safe applications of nanotechnology, still little is known about the biological interactions of many emerging 2D materials. Here, an investigation of how hexagonal boron nitride (hBN) in...
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Engineering::Nanotechnology Science::Biological sciences::Biophysics Engineering::Mathematics and analysis::Simulations Science::Medicine::Biomedical engineering Biomembranes Cell Uptake Lungs Molecular Dynamics Nanomaterials White Graphene |
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Engineering::Nanotechnology Science::Biological sciences::Biophysics Engineering::Mathematics and analysis::Simulations Science::Medicine::Biomedical engineering Biomembranes Cell Uptake Lungs Molecular Dynamics Nanomaterials White Graphene Lucherelli, Matteo Andrea Qian, Xuliang Weston, Paula Eredia, Matilde Zhu, Wenpeng Samorì, Paolo Gao, Huajian Bianco, Alberto von dem Bussche, Annette Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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While the interaction between 2D materials and cells is of key importance to the development of nanomedicines and safe applications of nanotechnology, still little is known about the biological interactions of many emerging 2D materials. Here, an investigation of how hexagonal boron nitride (hBN) interacts with the cell membrane is carried out by combining molecular dynamics (MD), liquid-phase exfoliation, and in vitro imaging methods. MD simulations reveal that a sharp hBN wedge can penetrate a lipid bilayer and form a cross-membrane water channel along its exposed polar edges, while a round hBN sheet does not exhibit this behavior. It is hypothesized that such water channels can facilitate cross-membrane transport, with important consequences including lysosomal membrane permeabilization, an emerging mechanism of cellular toxicity that involves the release of cathepsin B and generation of radical oxygen species leading to cell apoptosis. To test this hypothesis, two types of hBN nanosheets, one with a rhomboidal, cornered morphology and one with a round morphology, are prepared, and human lung epithelial cells are exposed to both materials. The cornered hBN with lateral polar edges results in a dose-dependent cytotoxic effect, whereas round hBN does not cause significant toxicity, thus confirming our premise. |
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School of Mechanical and Aerospace Engineering |
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School of Mechanical and Aerospace Engineering Lucherelli, Matteo Andrea Qian, Xuliang Weston, Paula Eredia, Matilde Zhu, Wenpeng Samorì, Paolo Gao, Huajian Bianco, Alberto von dem Bussche, Annette |
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Article |
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Lucherelli, Matteo Andrea Qian, Xuliang Weston, Paula Eredia, Matilde Zhu, Wenpeng Samorì, Paolo Gao, Huajian Bianco, Alberto von dem Bussche, Annette |
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Lucherelli, Matteo Andrea |
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Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization |
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2021 |
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https://hdl.handle.net/10356/152797 |
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sg-ntu-dr.10356-1527972021-12-10T12:34:33Z Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization Lucherelli, Matteo Andrea Qian, Xuliang Weston, Paula Eredia, Matilde Zhu, Wenpeng Samorì, Paolo Gao, Huajian Bianco, Alberto von dem Bussche, Annette School of Mechanical and Aerospace Engineering Institute of High Performance Computing, A*STAR University of Strasbourg, France Brown University, USA Sun Yat-sen University, China Engineering::Nanotechnology Science::Biological sciences::Biophysics Engineering::Mathematics and analysis::Simulations Science::Medicine::Biomedical engineering Biomembranes Cell Uptake Lungs Molecular Dynamics Nanomaterials White Graphene While the interaction between 2D materials and cells is of key importance to the development of nanomedicines and safe applications of nanotechnology, still little is known about the biological interactions of many emerging 2D materials. Here, an investigation of how hexagonal boron nitride (hBN) interacts with the cell membrane is carried out by combining molecular dynamics (MD), liquid-phase exfoliation, and in vitro imaging methods. MD simulations reveal that a sharp hBN wedge can penetrate a lipid bilayer and form a cross-membrane water channel along its exposed polar edges, while a round hBN sheet does not exhibit this behavior. It is hypothesized that such water channels can facilitate cross-membrane transport, with important consequences including lysosomal membrane permeabilization, an emerging mechanism of cellular toxicity that involves the release of cathepsin B and generation of radical oxygen species leading to cell apoptosis. To test this hypothesis, two types of hBN nanosheets, one with a rhomboidal, cornered morphology and one with a round morphology, are prepared, and human lung epithelial cells are exposed to both materials. The cornered hBN with lateral polar edges results in a dose-dependent cytotoxic effect, whereas round hBN does not cause significant toxicity, thus confirming our premise. Ministry of Education (MOE) Nanyang Technological University M.A.L. and X.Q. contributed equally to this work. The authors gratefully acknowledge the financial support from the EU Graphene Flagship project (No. 881603) and from the Agence Nationale de la Recherche (ANR) (ANR-15-GRFL-0001-05, G-Immunomics). H.G. acknowledges support from the Singapore Ministry of Education (MOE) under T1 Award #020565-00001. X.Q. and H.G. acknowledge support from a start-up grant from the Nanyang Technological University. X.Q. acknowledges support from the Presidential Fellowship from Brown University. This work was supported in part by ANR through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC). The authors wish to acknowledge the Centre National de la Recherche Scientifique (CNRS) and the International Center for Frontier Research in Chemistry (icFRC). Molecular dynamics simulations reported were performed on resources provided by the Center for Computation and Visualization at Brown University, the High Performance Computing Centre at Nanyang Technological University, Singapore, and the National Supercomputing Centre, Singapore (http://www.nscc.sg). The authors are indebted to Shi Guo and Fanny Richard for their help in sample preparation and XRD analyses, to Cathy Royer from the Plateforme Imagerie In Vitro de l'ITI Neurostra for SEM analyses, and to Islah El Masoudi for the ICP-MS measurements. 2021-12-10T12:34:32Z 2021-12-10T12:34:32Z 2021 Journal Article Lucherelli, M. A., Qian, X., Weston, P., Eredia, M., Zhu, W., Samorì, P., Gao, H., Bianco, A. & von dem Bussche, A. (2021). Boron nitride nanosheets can induce water channels across lipid bilayers leading to lysosomal permeabilization. Advanced Materials, 33(45), 2103137-. https://dx.doi.org/10.1002/adma.202103137 0935-9648 https://hdl.handle.net/10356/152797 10.1002/adma.202103137 34553436 2-s2.0-85115294711 45 33 2103137 en MOE T1 Award #020565-00001 ANR-15-GRFL-0001-05 EU Graphene Flagship project (No. 881603) ANR-10-LABX-0026_CSC Advanced Materials © 2021 Wiley-VCH GmbH. All righs reserved. |