Mechanical forces are key regulators of cell function with varying loads capable of modulating behaviors such as alignment, migration, phenotype modulation, and others. Historically, cell-stretching experiments have employed mechanically simple environments (e.g., uniform uniaxial or equibiaxial stretches). However, stretch distributions in vivo can be highly non-uniform, particularly in cases of disease or subsequent to interventional treatments. Herein, we present a cell-stretching device capable of subjecting cells to controllable gradients in biaxial stretch via radial deformation of circular elastomeric membranes. By including either a defect or a rigid fixation at the center of the membrane, various gradients are generated. Capabilities of the device were quantified by tracking marked positions of the membrane while applying various loads, and experimental feasibility was assessed by conducting preliminary experiments with 3T3 fibroblasts and 10T1/2 cells subjected to 24 h of cyclic stretch. Quantitative real-time PCR was used to measure changes in mRNA expression of a profile of genes representing the major smooth muscle phenotypes. Genes associated with the contractile state were both upregulated (e.g., calponin) and downregulated (e.g., α-2-actin), and genes associated with the synthetic state were likewise both upregulated (e.g., SKI-like oncogene) and downregulated (e.g., collagen III). In addition, cells aligned with an orientation perpendicular to the maximal stretch direction. We have developed an in vitro cell culture device that can produce non-uniform stretch environments similar to in vivo mechanics. Cells stretched with this device showed alignment and altered mRNA expression indicative of phenotype modulation. Understanding these processes as they relate to in vivo pathologies could enable a more accurately targeted treatment to heal or inhibit disease, either through implantable device design or pharmaceutical approaches.
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October 2011
Research Papers
A Device to Study the Effects of Stretch Gradients on Cell Behavior
William J. Richardson,
William J. Richardson
Department of Biomedical Engineering,
Texas A&M University
, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX
77843
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Richard P. Metz,
Richard P. Metz
Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center
, 336 Reynolds Medical Building, College Station, TX
77843
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Michael R. Moreno,
Michael R. Moreno
Department of Biomedical Engineering,
Texas A&M University
, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX
77843
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Emily Wilson,
Emily Wilson
Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center
, 336 Reynolds Medical Building, College Station, TX
77843
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James E. Moore, Jr.
James E. Moore, Jr.
Department of Biomedical Engineering,
Texas A&M University
, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX
77843
Search for other works by this author on:
William J. Richardson
Department of Biomedical Engineering,
Texas A&M University
, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX
77843
Richard P. Metz
Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center
, 336 Reynolds Medical Building, College Station, TX
77843
Michael R. Moreno
Department of Biomedical Engineering,
Texas A&M University
, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX
77843
Emily Wilson
Department of Systems Biology and Translational Medicine, Texas A&M Health Science Center
, 336 Reynolds Medical Building, College Station, TX
77843
James E. Moore, Jr.
Department of Biomedical Engineering,
Texas A&M University
, 337 Zachry Engineering Center, 3120 TAMU, College Station, TX
77843J Biomech Eng. Oct 2011, 133(10): 101008 (9 pages)
Published Online: November 1, 2011
Article history
Received:
June 15, 2011
Revised:
October 2, 2011
Online:
November 1, 2011
Published:
November 1, 2011
Citation
Richardson, W. J., Metz, R. P., Moreno, M. R., Wilson, E., and Moore, J. E., Jr. (November 1, 2011). "A Device to Study the Effects of Stretch Gradients on Cell Behavior." ASME. J Biomech Eng. October 2011; 133(10): 101008. https://doi.org/10.1115/1.4005251
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