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A Computational Approach to Understand Phenotypic Structure and Constitutive Mechanics Relationships of Single Cells

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Abstract

The goal of this study is to construct a representative 3D finite element model (FEM) of individual cells based on their sub-cellular structures that predicts cell mechanical behavior. The FEM simulations replicate atomic force microscopy (AFM) nanoindentation experiments on live vascular smooth muscle cells. Individual cells are characterized mechanically with AFM and then imaged in 3D using a spinning disc confocal microscope. Using these images, geometries for the FEM are automatically generated via image segmentation and linear programming algorithms. The geometries consist of independent structures representing the nucleus, actin stress fiber network, and cytoplasm. These are imported into commercial software for mesh refinement and analysis. The FEM presented here is capable of predicting AFM results well for 500 nm indentations. The FEM results are relatively insensitive to both the exact number and diameter of fibers used. Despite the localized nature of AFM nanoindentation, the model predicts that stresses are distributed in an anisotropic manner throughout the cell body via the actin stress fibers. This pattern of stress distribution is likely a result of the geometric arrangement of the actin network.

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Abbreviations

AFM:

Atomic force microscope

CytoD:

Cytochalasin D

FEM:

Finite element model

ST:

Simulation type

VSMC:

Vascular smooth muscle cell

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Acknowledgments

The authors would like to acknowledge the technical support provided by Shekhar Kanetkar and Zhong Qin of MSC Software and the financial support provided by the following grants from the National Institutes of Health: K25 HL 092228 and P20 RR-016461, and the National Science Foundation: CCF-0845593 and EPS-0903795.

Conflicts of interest

No conflict of interest apply to this manuscript and related work.

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Authors and Affiliations

  1. Department of Bioengineering, Clemson University, 301 Rhodes Research Center, Clemson, SC, 29634, USA

    Scott T. Wood & Delphine Dean

  2. School of Computing, Clemson University, 100 McAdams Hall, Clemson, SC, 29634, USA

    Brian C. Dean

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  1. Scott T. Wood
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Correspondence to Delphine Dean.

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Associate Editor Cheng Dong oversaw the review of this article.

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Wood, S.T., Dean, B.C. & Dean, D. A Computational Approach to Understand Phenotypic Structure and Constitutive Mechanics Relationships of Single Cells. Ann Biomed Eng 41, 630–644 (2013). https://doi.org/10.1007/s10439-012-0690-5

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