Research Papers

A Low-Cost Mechanical Stretching Device for Uniaxial Strain of Cells: A Platform for Pedagogy in Mechanobiology

[+] Author and Article Information
Hamza Atcha, Chase T. Davis, Nicholas R. Sullivan, Tim D. Smith, Sara Anis, Waleed Z. Dahbour, Zachery R. Robinson

Department of Biomedical Engineering,
The Edwards Lifesciences Center for
Advanced Cardiovascular Technology,
University of California Irvine,
Irvine, CA 92697

Anna Grosberg

Department of Biomedical Engineering,
Center for Complex Biological Systems,
The Edwards Lifesciences Center for
Advanced Cardiovascular Technology,
University of California Irvine,
Irvine, CA 92697;
Department of Chemical Engineering
and Materials Science,
University of California Irvine,
Irvine, CA 92697
e-mail: grosberg@uci.edu

Wendy F. Liu

Department of Biomedical Engineering,
The Edwards Lifesciences Center for
Advanced Cardiovascular Technology,
University of California Irvine,
Irvine, CA 92697;
Department of Chemical Engineering
and Materials Science,
University of California Irvine,
Irvine, CA 92697
e-mail: wendy.liu@uci.edu

1Corresponding authors.

Manuscript received January 11, 2018; final manuscript received March 30, 2018; published online May 24, 2018. Assoc. Editor: Kristen Billiar.

J Biomech Eng 140(8), 081005 (May 24, 2018) (9 pages) Paper No: BIO-18-1022; doi: 10.1115/1.4039949 History: Received January 11, 2018; Revised March 30, 2018

Mechanical cues including stretch, compression, and shear stress play a critical role in regulating the behavior of many cell types, particularly those that experience substantial mechanical stress within tissues. Devices that impart mechanical stimulation to cells in vitro have been instrumental in helping to develop a better understanding of how cells respond to mechanical forces. However, these devices often have constraints, such as cost and limited functional capabilities, that restrict their use in research or educational environments. Here, we describe a low-cost method to fabricate a uniaxial cell stretcher that would enable widespread use and facilitate engineering design and mechanobiology education for undergraduate students. The device is capable of producing consistent and reliable strain profiles through the use of a servomotor, gear, and gear rack system. The servomotor can be programmed to output various waveforms at specific frequencies and stretch amplitudes by controlling the degree of rotation, speed, and acceleration of the servogear. In addition, the stretchable membranes are easy to fabricate and can be customized, allowing for greater flexibility in culture well size. We used the custom-built stretching device to uniaxially strain macrophages and cardiomyocytes, and found that both cell types displayed functional and cell shape changes that were consistent with the previous studies using commercially available systems. Overall, this uniaxial cell stretcher provides a more cost-effective alternative to study the effects of mechanical stretch on cells, and can therefore, be widely used in research and educational environments to broaden the study and pedagogy of cell mechanobiology.

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Davies, P. F. , 1995, “ Flow-Mediated Endothelial Mechanotransduction,” Physiol. Rev., 75(3), pp. 519–560. [CrossRef] [PubMed]
Dhein, S. , Schreiber, A. , Steinbach, S. , Apel, D. , Salameh, A. , Schlegel, F. , Kostelka, M. , Dohmen, P. M. , and Mohr, F. W. , 2014, “ Mechanical Control of Cell Biology. Effects of Cyclic Mechanical Stretch on Cardiomyocyte Cellular Organization,” Prog. Biophys. Mol. Biol., 115(2–3), pp. 93–102. [CrossRef] [PubMed]
Okada, M. , Matsumori, A. , Ono, K. , Furukawa, Y. , Shioi, T. , Iwasaki, A. , Matsushima, K. , and Sasayama, S. , 1998, “ Cyclic Stretch Upregulates Production of Interleukin-8 and Monocyte Chemotactic and Activating Factor/Monocyte Chemoattractant Protein-1 in Human Endothelial Cells,” Arterioscler. Thromb. Vasc. Biol., 18(6), pp. 894–901. [CrossRef] [PubMed]
Pugin, J. , Dunn, I. , Jolliet, P. , Tassaux, D. , Magnenat, J.-L. , Nicod, L. P. , and Chevrolet, J.-C. , 1998, “ Activation of Human Macrophages by Mechanical Ventilation In Vivo,” Am. J. Physiol., 275(6), pp. L1040–L1050. [PubMed]
Naruse, K. , and Sokabe, M. , 1993, “ Involvement of Stretch-Activated Ion Channels in Ca2+ Mobilization to Mechanical Stretch in Endothelial Cells,” Am. J. Physiol., 264(4), pp. C1037–C1044. [CrossRef] [PubMed]
Ruwhof, C. , Wamel, A. E. T. V. , Egas, J. M. , and Laarse, A. V. D. , 2000, “ Cyclic Stretch Induces the Release of Growth Promoting Factors From Cultured Neonatal Cardiomyocytes and Cardiac Fibroblasts,” Mol. Cell. Biochem., 208(1/2), pp. 89–98. [CrossRef] [PubMed]
Miyauchi, A. , Gotoh, M. , Kamioka, H. , Notoya, K. , Sekiya, H. , Takagi, Y. , Yoshimoto, Y. , Ishikawa, H. , Chihara, K. , Takano-Yamamoto, T. , Fujita, T. , and Mikuni-Takagaki, Y. , 2006, “ αVβ3 Integrin Ligands Enhance Volume-Sensitive Calcium Influx in Mechanically Stretched Osteocytes,” J. Bone Miner. Metab., 24(6), pp. 498–504. [CrossRef] [PubMed]
VWR, 2018, “Cell Stretcher, Electron Microscopy Sciences,” VWR, Radnor, PA, accessed Jan. 10, 2018, https://us.vwr.com/store/product/12361336/cell-stretcher-electron-microscopy-sciences
Flexcell International Corporation, 2018, “ Flexcell Tension Systems,” Flexcell International Corporation, Burlington, NC, accessed Jan. 10, 2018, http://www.flexcellint.com/slideshow2.htm
Strex, 2018, “ Automated Cell Stretching System STB-140,” Strex Cell, San Diego, CA, accessed Jan. 10, 2018, https://strexcell.com/cell-stretching-system/models/automated-cell-stretching-system/
Cell Scale, 2018, “ MCFX,” CellScale, Ontario, Canada, accessed Jan. 10, 2018, http://cellscale.com/products/mcfx/
Lau, J. J. , Wang, R. M. , and Black, L. D. , 2014, “ Development of an Arbitrary Waveform Membrane Stretcher for Dynamic Cell Culture,” Ann. Biomed. Eng., 42(5), pp. 1062–1073. [CrossRef] [PubMed]
Toume, S. , Gefen, A. , and Weihs, D. , 2016, “ Printable Low-Cost, Sustained and Dynamic Cell Stretching Apparatus,” J. Biomech., 49(8), pp. 1336–1339. [CrossRef] [PubMed]
Yost, M. J. , Simpson, D. , Wrona, K. , Ridley, S. , Ploehn, H. J. , Borg, T. K. , and Terracio, L. , 2000, “ Design and Construction of a Uniaxial Cell Stretcher,” Am. J. Physiol., 279(6), pp. H3124–H3130.
Schürmann, S. , Wagner, S. , Herlitze, S. , Fischer, C. , Gumbrecht, S. , Wirth-Hücking, A. , Prölß, G. , Lautscham, L. , Fabry, B. , Goldmann, W. , Nikolova-Krstevski, V. , Martinac, B. , and Friedrich, O. , 2016, “ The IsoStretcher: An Isotropic Cell Stretch Device to Study Mechanical Biosensor Pathways in Living Cells,” Biosens. Bioelectron., 81(Suppl C), pp. 363–372. [CrossRef] [PubMed]
Singh, A. , 2017, “ A New Approach to Teaching Biomechanics Through Active, Adaptive, and Experiential Learning,” ASME J. Biomech. Eng., 139(7), p. 071001. [CrossRef]
Hadim, H. A. , and Esche, S. K. , 2002, “ Enhancing the Engineering Curriculum Through Project-Based Learning,” 32nd Annual Conference on Frontiers in Education., Vol. 2, pp. F3F-1–F3F-6.
Tiwari, A. , Lai, P. , So, M. , and Yuen, K. , 2006, “ A Comparison of the Effects of Problem-Based Learning and Lecturing on the Development of Students' Critical Thinking,” Med. Educ., 40(6), pp. 547–554. [CrossRef] [PubMed]
Gavin, K. , 2011, “ Case Study of a Project-Based Learning Course in Civil Engineering Design,” Eur. J. Eng. Educ., 36(6), pp. 547–558. [CrossRef]
Zydney, A. L. , Bennett, J. S. , Shahid, A. , and Bauer, K. W. , 2002, “ Impact of Undergraduate Research Experience in Engineering,” J. Eng. Educ., 91(2), pp. 151–157. [CrossRef]
Harding, T. S. , Vanasupa, L. , Savage, R. N. , and Stolk, J. D. , 2007, “ Work-in-Progress - Self-Directed Learning and Motivation in a Project-Based Learning Environment,” 37th Annual Frontiers in Education Conference on Global Engineering: Knowledge Without Borders, Opportunities Without Passports, pp. F2G-3–F2G-4.
Bell, S. , 2010, “ Project-Based Learning for the 21st Century: Skills for the Future,” The Clearing House, 83(2), pp. 39–43. [CrossRef]
Matsumoto, T. , Delafontaine, P. , Schnetzer, K. J. , Tong, B. C. , and Nerem, R. M. , 1996, “ Effect of Uniaxial, Cyclic Stretch on the Morphology of Monocytes/Macrophages in Culture,” ASME J. Biomech. Eng., 118(3), pp. 420–422. [CrossRef]
Matsuda, T. , Takahashi, K. , Nariai, T. , Ito, T. , Takatani, T. , Fujio, Y. , and Azuma, J. , 2004, “ N-Cadherin-Mediated Cell Adhesion Determines the Plasticity for Cell Alignment in Response to Mechanical Stretch in Cultured Cardiomyocytes,” Biochem. Biophys. Res. Commun., 326(1), pp. 228–232. [CrossRef]
Dziki, J. L. , Giglio, R. M. , Sicari, B. M. , Wang, D. S. , Gandhi, R. M. , Londono, R. , Dearth, C. L. , and Badylak, S. F. , 2017, “ The Effect of Mechanical Loading Upon Extracellular Matrix Bioscaffold-Mediated Skeletal Muscle Remodeling,” Tissue Eng. Part A, 24(1–2), pp. 34–46.
Kada, K. , Yasui, K. , Naruse, K. , Kamiya, K. , Kodama, I. , and Toyama, J. , 1999, “ Orientation Change of Cardiocytes Induced by Cyclic Stretch Stimulation: Time Dependency and Involvement of Protein Kinases,” J. Mol. Cell. Cardiol., 31(1), pp. 247–259. [CrossRef] [PubMed]
DebBurman, S. K. , 2002, “ Learning How Scientists Work: Experiential Research Projects to Promote Cell Biology Learning and Scientific Process Skills,” Cell Biol. Educ., 1(4), pp. 154–172. [CrossRef] [PubMed]
Mabrouk, P. A. , and Peters, K. , 2000, “ Student Perspectives on Undergraduate Research (UR) Experiences in Chemistry and Biology,” Cur. Q., 21(1), pp. 25–33. https://confchem.ccce.divched.org/2000SpringConfChemP2
Wendy Liu Lab Organization, 2018, “ Uniaxial Cell Stretcher,” Wendy Liu Lab Organization, Cambridge, MA, accessed Feb. 23, 2018, https://figshare.com/s/a6b93d33635fbce8471e
Stuurman, N. , Schindelin, J. , Elliot, C. , and Hiner, M. , 2017, “ MTrack2-2.0.1,” Github Repository, San Francisco, CA, ImageJ, accessed Jan. 10, 2018, https://github.com/fiji/MTrack2/releases/tag/MTrack2_-2.0.1
Wendy Liu Lab Organization, 2018, “ Pinscreen: Simple Optical Strain Tracking Calibration,” Github Repository, San Francisco, CA, accessed Jan. 10, 2018, https://github.com/WendyLiuLab/pinscreen
Knight, M. B. , Drew, N. K. , McCarthy, L. A. , and Grosberg, A. , 2016, “ Emergent Global Contractile Force in Cardiac Tissues,” Biophys. J., 110(7), pp. 1615–1624. [CrossRef] [PubMed]
Drew, N. K. , Johnsen, N. E. , Core, J. Q. , and Grosberg, A. , 2016, “ Multiscale Characterization of Engineered Cardiac Tissue Architecture,” ASME J. Biomech. Eng., 138(11), p. 111003. [CrossRef]
Drew, N. K. , Eagleson, M. A. , K. K., Jr , B, D. B. , Parker ., and Grosberg, A. , 2015, “ Metrics for Assessing Cytoskeletal Orientational Correlations and Consistency,” PLoS Comput. Biol., 11(4), p. e1004190. [CrossRef] [PubMed]
McCain, M. L. , Sheehy, S. P. , Grosberg, A. , Goss, J. A. , and Parker, K. K. , 2013, “ Recapitulating Maladaptive, Multiscale Remodeling of Failing Myocardium on a Chip,” Proc,” Natl. Acad. Sci., 110(24), pp. 9770–9775. [CrossRef]
Liu, X. , Ensenat, D. , Wang, H. , Schafer, A. I. , and Durante, W. , 2003, “ Physiologic Cyclic Stretch Inhibits Apoptosis in Vascular Endothelium,” FEBS Lett., 541(1–3), pp. 52–56. [CrossRef] [PubMed]
Dandel, M. , Lehmkuhl, H. , Knosalla, C. , Suramelashvili, N. , and Hetzer, R. , 2009, “ Strain and Strain Rate Imaging by Echocardiography—Basic Concepts and Clinical Applicability,” Curr. Cardiol. Rev., 5(2), pp. 133–148. [CrossRef] [PubMed]
Dartsch, P. C. , Hämmerle, H. , and Betz, E. , 1986, “ Orientation of Cultured Arterial Smooth Muscle Cells Growing on Cyclically Stretched Substrates,” Cells Tissues Organs, 125(2), pp. 108–113. [CrossRef]
Kanda, K. , Matsuda, T. , and Oka, T. , 1992, “ Two-Dimensional Orientational Response of Smooth Muscle Cells to Cyclic Stretching,” ASAIO J., 38(3), pp. M382–M385. http://europepmc.org/abstract/med/1457887 [PubMed]
Kanda, K. , and Matsuda, T. , 1993, “ Behavior of Arterial Wall Cells Cultured on Periodically Stretched Substrates,” Cell Transplant., 2(6), pp. 475–484. [CrossRef] [PubMed]
Houtchens, G. R. , Foster, M. D. , Desai, T. A. , Morgan, E. F. , and Wong, J. Y. , 2008, “ Combined Effects of Microtopography and Cyclic Strain on Vascular Smooth Muscle Cell Orientation,” J. Biomech., 41(4), pp. 762–769. [CrossRef] [PubMed]
Balestrini, J. L. , Skorinko, J. K. , Hera, A. , Gaudette, G. R. , and Billiar, K. L. , 2010, “ Applying Controlled Non-Uniform Deformation for In Vivo Studies of Cell Mechanobiology,” Biomech. Model. Mechanobiol., 9(3), pp. 329–344. [CrossRef] [PubMed]
Salameh, A. , Wustmann, A. , Karl, S. , Blanke, K. , Apel, D. , Rojas-Gomez, D. , Franke, H. , Mohr, F. W. , Janousek, J. , and Dhein, S. , 2010, “ Cyclic Mechanical Stretch Induces Cardiomyocyte Orientation and Polarization of the Gap Junction Protein Connexin43,” Circ. Res., 106(10), pp. 1592–1602. [CrossRef] [PubMed]
De, R. , Zemel, A. , and Safran, S. A. , 2007, “ Dynamics of Cell Orientation,” Nat. Phys., 3(9), pp. 655–659. [CrossRef]
Kardash, C. M. , 2000, “ Evaluation of Undergraduate Research Experience: Perceptions of Undergraduate Interns and Their Faculty Mentors,” J. Educ. Psychol., 92(1), p. 191. [CrossRef]


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Fig. 1

Design of uniaxial cell stretching device. (a) Three-dimensional schematic of uniaxial cell stretching device (left) including a cross section and expanded view (right) to better display the gear and gear rack mechanism for mechanical motion as well as the clamping mechanism used to maintain substrate tension. The device consists of a 6061-T6 aluminum housing (transparent), programmable servomotor (1), 0.635 cm (0.25 in) rails (2), moveable middle clamps (3), experimental substrates (4), stationary side clamps (5), wing nuts (6), top clamps (7), a silicone sheet to balance the experimental substrates (8), 0.635 cm (0.25 in) in threaded rods (9), gear (10), gear rack (11), and 0.635 cm (0.25 in) 0.25 in shaft support (12). (b) Schematic of unstrained (left), static strain (middle), and cyclic strain (right) configurations of the device.

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Fig. 2

Validation of uniaxial cell stretcher. (a) The designed cell stretcher is capable of generating a 1 Hz triangle, sine, or square wave through manipulating various speed and acceleration parameters. (b) Measured strains in both the directions parallel and perpendicular to stretch were quantified and were found to be uniform and consistent with the desired 10% and 20% strains.

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Fig. 3

Macrophages align and elongate in response to 10% cyclic strain. (a) Phase contrast images of unstimulated (top) and IFN-γ/LPS (bottom) stimulated macrophages cultured under either 0% (left) or 10% (right) cyclic stretch. Arrow indicates the direction of stretch. (b) Quantification of OOP and (c) aspect ratio as a measure of macrophage alignment and elongation in response to cyclic stretch, respectively. Error bars indicate standard deviation of the mean for three separate experiments and * denotes p < 0.05 when compared to the 0% stretch condition as determined by student's t-test.

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Fig. 4

Macrophage inflammatory cytokine secretion is unaffected by 10% cyclic uniaxial stretch. Secretion of TNF-α (left), IL-6 (middle), and MCP-1 (right) for unstimulated and IFN-γ/LPS stimulated macrophages subjected to either 0% or 10% cyclic uniaxial stretch. Data are normalized to IFN-γ/LPS stimulated and stretched condition. Error bars indicate standard deviation of the mean for three separate experiments.

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Fig. 5

Cardiomyocytes align in response to cyclic uniaxial stretch. (a) NRVMs after 6 h of cyclic stretching and stained for actin (green, horizontal lines), sarcomeric z-lines (red, vertical lines), and nuclei (blue, circular structures). There is qualitative alignment in the direction of stretch (white arrow). (b) The orientational order parameter of the actin fibrils from the stretch tissues compared to the previously published data [33] for isotropic and anisotropic tissues shows that 6 h of stretch produces significant alignment. Error bars indicate standard deviation about the mean for at least three separate experiments and * denotes p < 0.01 determined by one-way ANOVA Tukey.



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