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Mechanical Interactions of Mouse Mammary Gland Cells with Collagen in a Three-Dimensional Construct

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Abstract

An effort to understand the development of breast cancer motivates the study of mammary gland cells and their interactions with the extracellular matrix. A mixture of mammary gland epithelial cells (normal murine mammary gland), collagen, and fluorescent beads was loaded into microchannels and observed via four-dimensional imaging. Collagen concentrations of 1.3, 2, and 3 mg/mL were used. The displacements of the beads were used to calculate strains in the 3D matrix. To ensure physiologically relevant materials properties for analysis, the collagen was characterized using independent tensile testing with strain rates in the range of those measured in the cell–gel constructs. 3D elastic theory for an isotropic material was employed to calculate the stress. The technique presented adds to the field of measuring cell-generated stresses by providing the capability of measuring 3D stresses locally around a single cell and using physiologically relevant materials properties for analysis. The highest strains were observed in the most compliant matrix. Additionally, the stresses fluctuated over time due to the cells’ interaction with the collagen matrix.

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Abbreviations

E :

Young’s modulus (kPa)

\( \dot{\varepsilon } \) :

Strain rate (min−1)

ε :

Strain (μm/μm)

u :

Displacement (mm)

Δx :

Original distance in x (μm)

Δx′:

New distance in x (μm)

σ :

Stress (Pa)

C :

Elastic modulus matrix (kPa)

G :

First Lame elastic parameter and shear modulus (kPa)

λ :

Second Lame elastic parameter (kPa)

ν :

Poisson’s ratio (dimensionless)

Δt :

Change in time (min)

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Acknowledgments

The authors would like to thank Patricia Keely’s lab at the University of Wisconsin – Madison for allowing the use of their microscope, especially Dr. Matt Conklin for his time and assistance and Prof. Keely for helpful conversations. The authors would also like to thank Erich Zeiss for all of his help with the imaging and use of Slidebook software. This work was possible via funding from the Harriet Jenkins Pre-doctoral Fellowship (JPFP-NASA); Graduate Engineering Research Scholars (GERS) of the College of Engineering, University of Wisconsin – Madison; and the Ruth Dickie Research Scholarship from the University of Wisconsin Beta Chapter of Sigma Delta Epsilon-Graduate Women in Science (SDE-GWIS).

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Authors and Affiliations

  1. Material Science Program, Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, WI, USA

    M. d. C. Lopez-Garcia

  2. Department of Biomedical Engineering, Wisconsin Institutes for Medical Research, University of Wisconsin, Madison, WI, USA

    D. J. Beebe

  3. Department of Engineering Physics, University of Wisconsin – Madison, 543 Engineering Research Building, 1500 Engineering Dr, Madison, WI, 53706, USA

    W. C. Crone

Authors
  1. M. d. C. Lopez-Garcia
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  2. D. J. Beebe
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  3. W. C. Crone
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Correspondence to W. C. Crone.

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Associate Editor Jennifer West oversaw the review of this article.

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Lopez-Garcia, M.d.C., Beebe, D.J. & Crone, W.C. Mechanical Interactions of Mouse Mammary Gland Cells with Collagen in a Three-Dimensional Construct. Ann Biomed Eng 38, 2485–2498 (2010). https://doi.org/10.1007/s10439-010-0015-5

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