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Magnification of Cholesterol-Induced Membrane Resistance on the Tissue Level: Implications for Hypoxia

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Oxygen Transport to Tissue XXXVIII

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 923))

Abstract

High cellular membrane cholesterol is known to generate membrane resistance and reduce oxygen (O2) permeability. As such, cholesterol may contribute to the Warburg effect in tumor cells by stimulating intracellular hypoxia that cannot be detected from extracellular oxygen measurements. We probe the tissue-level impact of the phenomenon, asking whether layering of cells can magnify the influence of cholesterol, to modulate hypoxia in relation to capillary proximity. Using molecular dynamics simulations, we affirm that minimally hydrated, adjacent lipid bilayers have independent physical behavior. Combining this insight with published experimental data, we predict linearly increasing impact of membrane cholesterol on oxygen flux across cells layered in tissue.

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Acknowledgments

Financial support for this project was provided by the NM-INBRE program, which is funded by National Institutes of Health grant P20GM103451 through NIGMS. Further financial support was generously provided by the Glendorn Foundation. The project used computing resources of the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by National Science Foundation grant number ACI-1053575. We thank Snežna Rogelj for her ongoing inspiration and biological insight, Jeff Altig for helpful conversations, and Ryan Bredin for developing our O2 force field parameters. We gratefully acknowledge Ross Walker and Benjamin Madej for providing advance access to their updated cholesterol force field parameters. Finally, we appreciate the thoughtful review of our manuscript by members of the International Society on Oxygen Transport to Tissue (ISOTT).

Author information

Authors and Affiliations

  1. Department of Chemistry, New Mexico Institute of Mining and Technology (New Mexico Tech), 801 Leroy Place, Socorro, NM, 87801, USA

    Ryan Shea, Casey Smith & Sally C. Pias

  2. Department of Mathematics, Chemistry, and Physics, West Texas A&M University, Canyon, TX, USA

    Ryan Shea

Authors
  1. Ryan Shea
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  2. Casey Smith
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  3. Sally C. Pias
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Corresponding author

Correspondence to Sally C. Pias .

Editor information

Editors and Affiliations

  1. Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China

    Qingming Luo

  2. Molecular Imaging Laboratory, Department of Radiology, Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Lin Z. Li

  3. Microvascular Measurements, St. Lorenzen, Italy

    David K. Harrison

  4. Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China

    Hua Shi

  5. ISOTT Historian, Ellicott City, Maryland, USA

    Duane F. Bruley

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© 2016 Springer International Publishing Switzerland

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Shea, R., Smith, C., Pias, S.C. (2016). Magnification of Cholesterol-Induced Membrane Resistance on the Tissue Level: Implications for Hypoxia. In: Luo, Q., Li, L., Harrison, D., Shi, H., Bruley, D. (eds) Oxygen Transport to Tissue XXXVIII. Advances in Experimental Medicine and Biology, vol 923. Springer, Cham. https://doi.org/10.1007/978-3-319-38810-6_6

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