C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages
C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages
There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.
4134-4144
Russ, K.A.
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Elvati, P.
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Parsonage, Tina, Louise
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Dews, A.
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Jarvis, J.A.
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Ray, M.
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Schneider, B.
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Smith, P.J.S.
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Williamson, P.T.F.
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Violi, A.
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Philbert, M.A.
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2016
Russ, K.A.
76de9de1-f1c0-4086-9b4d-06bc11212e51
Elvati, P.
40a22547-9c48-4aa1-ad2b-5dc8f37b44ca
Parsonage, Tina, Louise
652160d8-72de-4846-a644-e9de62276706
Dews, A.
4319d2bf-d27e-443b-ae14-cb0a39f0f9dd
Jarvis, J.A.
d88eea9b-525e-40f9-ab4a-98d12b7fe7ac
Ray, M.
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Schneider, B.
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Smith, P.J.S.
003de469-9420-4f12-8f0e-8e8d76d28d6c
Williamson, P.T.F.
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Violi, A.
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Philbert, M.A.
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Russ, K.A., Elvati, P., Parsonage, Tina, Louise, Dews, A., Jarvis, J.A., Ray, M., Schneider, B., Smith, P.J.S., Williamson, P.T.F., Violi, A. and Philbert, M.A.
(2016)
C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages.
Nanoscale, 8 (7), .
(doi:10.1039/c5nr07003a).
Abstract
There continues to be a significant increase in the number and complexity of hydrophobic nanomaterials that are engineered for a variety of commercial purposes making human exposure a significant health concern. This study uses a combination of biophysical, biochemical and computational methods to probe potential mechanisms for uptake of C60 nanoparticles into various compartments of living immune cells. Cultures of RAW 264.7 immortalized murine macrophage were used as a canonical model of immune-competent cells that are likely to provide the first line of defense following inhalation. Modes of entry studied were endocytosis/pinocytosis and passive permeation of cellular membranes. The evidence suggests marginal uptake of C60 clusters is achieved through endocytosis/pinocytosis, and that passive diffusion into membranes provides a significant source of biologically-available nanomaterial. Computational modeling of both a single molecule and a small cluster of fullerenes predicts that low concentrations of fullerenes enter the membrane individually and produce limited perturbation; however, at higher concentrations the clusters in the membrane causes deformation of the membrane. These findings are bolstered by nuclear magnetic resonance (NMR) of model membranes that reveal deformation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape of the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. The surprising contribution of passive modes of cellular entry provides new avenues for toxicological research that go beyond the pharmacological inhibition of bulk transport systems such as pinocytosis.
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Accepted/In Press date: 21 January 2016
e-pub ahead of print date: 25 January 2016
Published date: 2016
Organisations:
Faculty of Natural and Environmental Sciences, Optoelectronics Research Centre
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Local EPrints ID: 387905
URI: http://eprints.soton.ac.uk/id/eprint/387905
ISSN: 2040-3364
PURE UUID: e64649b5-31ef-4e16-b5e1-f3c6cca98b44
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Date deposited: 17 Feb 2016 11:33
Last modified: 15 Mar 2024 03:39
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Contributors
Author:
K.A. Russ
Author:
P. Elvati
Author:
Tina, Louise Parsonage
Author:
A. Dews
Author:
J.A. Jarvis
Author:
M. Ray
Author:
B. Schneider
Author:
A. Violi
Author:
M.A. Philbert
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