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Title: C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages

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. Compu-tational 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 defor-mation of the cell membrane upon exposure to high concentrations of fullerenes. The atomistic and NMR models fail to explain escape ofmore » the particle out of biological membranes, but are limited to idealized systems that do not completely recapitulate the complexity of cell membranes. Lastly, 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.« less

Authors:
 [1];  [2];  [3];  [1];  [3];  [1];  [1];  [3];  [3];  [4];  [1]
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  1. Univ. of Michigan, Ann Arbor, MI (United States). Toxicology Program, School of Public Health
  2. Univ. of Michigan, Ann Arbor, MI (United States). Mechanical Engineering
  3. Univ. of Southampton (United Kingdom). Centre for Biological Science, and Inst. for Life Sciences
  4. Univ. of Michigan, Ann Arbor, MI (United States). Mechanical Engineering; Univ. of Michigan, Ann Arbor, MI (United States). Chemical Engineering, Biomedical Engineering, Biophysics
Publication Date:
Research Org.:
Univ. of Michigan, Ann Arbor, MI (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
OSTI Identifier:
1435722
Grant/Contract Number:  
SC0002619
Resource Type:
Accepted Manuscript
Journal Name:
Nanoscale
Additional Journal Information:
Journal Volume: 8; Journal Issue: 7; Journal ID: ISSN 2040-3364
Publisher:
Royal Society of Chemistry
Country of Publication:
United States
Language:
English
Subject:
77 NANOSCIENCE AND NANOTECHNOLOGY; 59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Russ, K. A., Elvati, P., Parsonage, T. L., Dews, A., Jarvis, J. A., Ray, M., Schneider, B., Smith, P. J. S., Williamson, P. T. F., Violi, A., and Philbert, M. A. C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages. United States: N. p., 2016. Web. doi:10.1039/c5nr07003a.
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Russ, K. A., Elvati, P., Parsonage, T. L., Dews, A., Jarvis, J. A., Ray, M., Schneider, B., Smith, P. J. S., Williamson, P. T. F., Violi, A., & Philbert, M. A. C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages. United States. https://doi.org/10.1039/c5nr07003a
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Russ, K. A., Elvati, P., Parsonage, T. L., Dews, A., Jarvis, J. A., Ray, M., Schneider, B., Smith, P. J. S., Williamson, P. T. F., Violi, A., and Philbert, M. A. Fri . "C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages". United States. https://doi.org/10.1039/c5nr07003a. https://www.osti.gov/servlets/purl/1435722.
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@article{osti_1435722,
title = {C60 fullerene localization and membrane interactions in RAW 264.7 immortalized mouse macrophages},
author = {Russ, K. A. and Elvati, P. and Parsonage, T. L. and Dews, A. and Jarvis, J. A. and Ray, M. and Schneider, B. and Smith, P. J. S. and Williamson, P. T. F. and Violi, A. and Philbert, M. A.},
abstractNote = {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. Compu-tational 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 defor-mation 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. Lastly, 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.},
doi = {10.1039/c5nr07003a},
journal = {Nanoscale},
number = 7,
volume = 8,
place = {United States},
year = {Fri Jan 01 00:00:00 EST 2016},
month = {Fri Jan 01 00:00:00 EST 2016}
}
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Journal Article:
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https://doi.org/10.1039/c5nr07003a
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Cited by: 52 works
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Figures / Tables:

Fig. 1 Fig. 1: Characterization of C60 fullerenes and terbium-endohedral fullerenes. Nanosight analysis of C60 fullerenes and Tb@C60 aggregate size: C60 fullerene aggregates were approximately 55.179 nm with a standard deviation of 34.16 nm. Tb@C60 aggregates were approximately 63.765 nm with a standard deviation of 24.46 nm.
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    Works referencing / citing this record:

    Toxicity of C60 fullerene–cisplatin nanocomplex against Lewis lung carcinoma cells
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