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Research Papers

Cell-to-Cell Variability in Deformations Across Compressed Myoblasts

[+] Author and Article Information
Noa Slomka

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

Amit Gefen1

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

Effective material property means that this property weighs together the stiffness contributions of components at sub-scale of the structure; for example, the effective shear modulus of the cytoplasm weighs together the stiffness contributions of the cytosol, cytoskeleton, and all other organelles (excluding the nucleus that is represented separately herein).

1

Corresponding author.

J Biomech Eng 133(8), 081007 (Sep 15, 2011) (6 pages) doi:10.1115/1.4004864 History: Received March 08, 2011; Accepted August 13, 2011; Published September 15, 2011; Online September 15, 2011

Many biological consequences of external mechanical loads applied to cells depend on localized cell deformations rather than on average whole-cell-body deformations. Such localized intracellular deformations are likely to depend, in turn, on the individual geometrical features of each cell, e.g., the local surface curvatures or the size of the nucleus, which always vary from one cell to another, even within the same culture. Our goal here was to characterize cell-to-cell variabilities in magnitudes and distribution patterns of localized tensile strains that develop in the plasma membrane (PM) and nuclear surface area (NSA) of compressed myoblasts, in order to identify resemblance or differences in mechanical performances across the cells. For this purpose, we utilized our previously developed confocal microscopy-based three-dimensional cell-specific finite element modeling methodology. Five different C2C12 undifferentiated cells belonging to the same culture were scanned confocally and modeled, and were then subjected to compression in the simulation setting. We calculated the average and peak tensile strains in the PM and NSA, the percentage of PM area subjected to tensile strains above certain thresholds and the coefficient of variation (COV) in average and peak strains. We found considerable COV values in tensile strains developing at the PM and NSA (up to ∼35%) but small external compressive deformations induced greater variabilities in intracellular strains across cells compared to large deformations. Interestingly, the external deformations needed to cause localized PM or NSA strains exceeding each threshold were very close across the different cells. Better understanding of variabilities in mechanical performances of cells—either of the same type or of different types—is important for interpreting experimental data in any experiments involving delivery of mechanical loads to cells.

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Copyright © 2011 by American Society of Mechanical Engineers
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Figures

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Figure 1

An example of the process of cell-specific three-dimensional (3D) finite element (FE) modeling: (a) One z-stack image of a FITC-labeled Phalloidin-stained myoblast (cell A), and confocal projections of the cell to the xz and zy planes (side views). (b) Top view of the 3D solid model of cell A, built from the z-stack of its confocal images, with corresponding projections to the xz and zy planes. (c) The FE mesh of cell A. (d) Top views of the distributions of tensile strains in the plasma membranes of all the five cells modeled herein, for a global cell deformation (GCD) of 55%.

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Figure 2

Average (top row) and peak (bottom row) tensile strains in the plasma membrane (PM) [(a), (c)] and nuclear surface area (NSA) [(b), (d)] for the five compressed cells. The data shown were calculated by fitting 2nd-order polynomial functions to the discrete strain versus global cell deformation (GCD) data points provided by the finite element simulations, and then averaging the values of the fits obtained for each cell, per each GCD level. Error bars are standard deviations around the mean value.

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Figure 3

Coefficients of variation in average and peak strains in (a) the plasma membrane (PM) and (b) the nuclear surface area (NSA) versus the global cell deformation (GCD), across the five cells

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Figure 4

Percentage of plasma membrane (PM) area (left column) and nuclear surface area (NSA) (right column) subjected to tensile strain values exceeding [(a), (b)] 5%, [(c), (d)] 15%, and [(e), (f)] 25% versus the global cell deformation (GCD)

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Figure 5

Magnitudes of the minimal tensile strains that will develop in the plasma membrane (PM) and nuclear surface area (NSA) for each global cell deformation (GCD) that is externally applied to deform the cell

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