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

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.

doi:10.1039/c5nr07003a

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

Journal Article · Fri Jan 01 00:00:00 EST 2016 · Nanoscale

DOI:https://doi.org/10.1039/c5nr07003a· OSTI ID:1435722

Russ, K. A. ^[1]; Elvati, P. ^[2]; Parsonage, T. L. ^[3]; Dews, A. ^[1]; Jarvis, J. A. ^[3]; Ray, M. ^[1]; Schneider, B. ^[1]; Smith, P. J. S. ^[3]; Williamson, P. T. F. ^[3]; Violi, A. ^[4]; Philbert, M. A. ^[1]

Univ. of Michigan, Ann Arbor, MI (United States). Toxicology Program, School of Public Health
Univ. of Michigan, Ann Arbor, MI (United States). Mechanical Engineering
Univ. of Southampton (United Kingdom). Centre for Biological Science, and Inst. for Life Sciences
Univ. of Michigan, Ann Arbor, MI (United States). Mechanical Engineering; Univ. of Michigan, Ann Arbor, MI (United States). Chemical Engineering, Biomedical Engineering, Biophysics

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.

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Research Organization:: Univ. of Michigan, Ann Arbor, MI (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)

Grant/Contract Number:: SC0002619

OSTI ID:: 1435722

Journal Information:: Nanoscale, Vol. 8, Issue 7; ISSN 2040-3364

Publisher:: Royal Society of ChemistryCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 52 works

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