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Technical Briefs

Stretching Affects Intracellular Oxygen Levels: Three-Dimensional Multiphysics Studies

[+] Author and Article Information
Efrat Leopold

Faculty of Engineering, Department of Biomedical Engineering,  Tel Aviv University, Tel Aviv 69978, Israel

Amit Gefen1

Faculty of Engineering, Department of Biomedical Engineering,  Tel Aviv University, Tel Aviv 69978, Israelgefen@eng.τ.ac.il

It is straight-forward to demonstrate this phenomenon if idealizing the shape of a cultured cell as a disk, for which model it can then be shown that the ratio of the undeformed over the deformed surface areas is approximately the squared ratio of the radii of the undeformed over the deformed (disk-shaped) cell. This ratio must be less than unity for the disk cell model; hence, the deformed surface area is greater, which means that more surface area is available for O2 transport in the deformed configuration.

1

Corresponding author.

J Biomech Eng 134(6), 064501 (Jun 08, 2012) (8 pages) doi:10.1115/1.4006813 History: Received April 22, 2012; Revised May 04, 2012; Posted May 11, 2012; Published June 08, 2012; Online June 08, 2012

Multiphysics modeling is an emerging approach in cellular bioengineering research, used for simulating complex biophysical interactions and their effects on cell viability and function. Our goal in the present study was to integrate cell-specific finite element modeling—which we have developed in previous research to simulate deformation of individual cells subjected to external loading—with oxygen transport in the deformed cells at normoxic and hypoxic environments. We specifically studied individual and combined effects of substrate stretch levels, O2 concentration in the culture media, and temperature of the culture media on intracellular O2 levels in cultured myoblasts, in models of two individual cells. We found that (i) O2 transport became faster with the increasing levels of substrate stretch (ranging from 0 to 24%), and (ii) the effect of a 3  °C temperature drop on slowing down the O2 transport was milder with respect to the effect that strains had. The changes in cell geometry due to externally applied deformations could, hence, theoretically affect cell respiration, which should be a consideration in cellular mechanics experiments.

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Copyright © 2012 by American Society of Mechanical Engineers
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Figures

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Figure 1

The surface geometries of cells A and B (undeformed condition), reconstructed in the Virtual Cell software. Each cell model also contains a nucleus (not shown).

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Figure 2

Finite element simulations of the radial stretching of cell B: Deformed shapes and strain distributions across the plasma membrane (left column) and the nucleus (right column)

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Figure 3

Example oxygen concentration distributions at time t = 0.008 s in the cytosol of cell A, at the undeformed state (top frames) and deformed state, where the substrate is being stretched to 24% strain (bottom frames). The left and right frames per each deformation condition show O2 distributions at the inferior surface of the cell and at an additional, horizontal cross-section around the inferior nuclear surface, respectively.

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Figure 4

Mean oxygen concentration curves within (a) the cytosol (COC(t), Eq. 5)) and (b) the nucleus (NOC(t), Eq. 6) for cell A, for different substrate strain levels at the 0–24% strain range and for a medium temperature of 37 °C

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Figure 5

Mean oxygen concentration curves within (a) the cytosol and (b) the nucleus for cell A, for different substrate strain levels at the 0–24% strain range, when there is no oxygen in the medium and for a medium temperature of 37 °C

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Figure 6

Time coefficients τ of the exponential fits to time courses of intracellular oxygen concentrations in (a) the cytosol and (b) the nucleus of cells A and B, where the Cmedium (t = 0) was either 0.02 μM or 1 μM, and at media temperatures of 34 °C or 37 °C. These data show faster O2 diffusion into the cytosol and nucleus (i.e., lower τ values) with: (i) increasing levels of substrate strain, (ii) higher temperature of the medium, and (3) decrease in the Cmedium (t = 0)–Cc (t = 0) gradient.

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Figure 7

Time coefficients β of the exponential fits to time courses of intracellular oxygen concentrations in (a) the cytosol and (b) the nucleus of cells A and B, when there is no oxygen in the medium, and for media temperatures of 34 °C or 37 °C. These data show faster O2 diffusion out of the cytosol and nucleus (i.e., higher β values) with: (i) increasing levels of substrate strain and (ii) higher temperature of the medium.

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