Skip to main content
SpringerLink
Log in

Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

Mechanical effects on cells have received more and more attention in the studies of tissue engineering, cellular pathogenesis, and biomedical device design. Anisotropic biaxial cyclic stress, reminiscent of the in vivo cellular mechanical environment, may promise significant implications for biotechnology and human health. We have designed, fabricated and characterized a microdevice that imparts a variety of anisotropic biaxial cyclic strain gradients upon cells. The device is composed of an elastic membrane with microgroove patterns designed to associate cell orientation axes with biaxial strain vectors on the membrane and a Flexcell stretcher with timely controlled vacuum pressure. The stretcher generates strain profile of anisotropic biaxial microgradients on the membrane. Cell axes determined by the microgrooves are associated with the membrane strain profile to impose proper biaxial strains on cells. Using vascular smooth muscle cells as a cell model, we demonstrated that the strain anisotropy index of a cell was likely one of the determinant mechanical factors in cell structural and functional adaptations. The nuclear shape and cytoskeleton structure of smooth muscle cells were influenced by mechanical loading, but were not significantly affected by the strain anisotropy. However, cell proliferation has profound responses to strain anisotropy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • ABAQUS/Standard User’s Manual, Ver. 6.4, Vol.II. Hibbitt, Karlson & Sorensen, Inc. 2001

  • G.H. Altman, R.L. Horan, I. Martin, J. Farhadi, P.R. Stark, V. Volloch et al., Cell differentiation by mechanical stress FASEB J. 16, 270–272 (2002)

    Google Scholar 

  • A.E. Baer, T.A. Laursen, F. Guilak, L.A. Setton, The micromechanical environment of intervertebral disc cells determined by a finite deformation, anisotropic, and biphasic finite element model J. Biomech. Eng. 125, 1–11 (2003), doi:10.1115/1.1532790

    Article  Google Scholar 

  • T.D. Brown, Techniques for mechanical stimulation of cells in vitro: a review J. Biomech. 33, 3–14 (2000), doi:10.1016/S0021-9290(99)00177-3

    Article  Google Scholar 

  • P. Camelliti, A.D. McCulloch, P. Kohl, Microstructured cocultures of cardiac myocytes and fibroblasts: a two-dimensional in vitro model of cardiac tissue Microsc. Microanal. 11, 249–259 (2005), doi:10.1017/S1431927605050506

    Article  Google Scholar 

  • P. Camelliti, J.O. Gallagher, P. Kohl, A.D. McCulloch, Micropatterned cell cultures on elastic membranes as an in vitro model of myocardium Nat. Protocols 1, 1379–1391 (2006). doi:10.1038/nprot.2006.203

    Article  Google Scholar 

  • M. Cayouette, M. Raff, The orientation of cell division influences cell-fate choice in the developing mammalian retina Development 130, 2329–2339 (2003), doi:10.1242/dev.00446

    Article  Google Scholar 

  • C. Clark, T. Burkholder, J. Frangos, Uniaxial strain system to investigate strain rate regulation in vitro Rev. Sci. Instrum. 72, 2415–2422 (2001). doi:10.1063/1.1362440

    Article  Google Scholar 

  • N. Dard, S. Louvet, A. Santa-Maria, J. Aghion, M. Martin, P. Mangeat et al., In vivo functional analysis of ezrin during mouse blastocyst formation Dev. Biol. 233, 161–173 (2001), doi:10.1006/dbio.2001.0192

    Article  Google Scholar 

  • P.F. Davies, J.A. Spaan, R. Krams, Shear stress biology of the endothelium Ann. Biomed. Eng. 33, 1714–1718 (2005), doi:10.1007/s10439-005-8774-0

    Article  Google Scholar 

  • M.T. Draney, F.R. Arko, M.T. Alley, M. Markl, R.J. Herfkens, N.J. Pelc et al., Quantification of vessel wall motion and cyclic strain using cine phase contrast MRI: in vivo validation in the porcine aorta Magn. Reson. Med 52, 286–295 (2004), doi:10.1002/mrm.20137

    Article  Google Scholar 

  • G.A. Dunn, A.F. Brown, Alignment of fibroblasts on grooved surfaces described by a simple geometric transformation J. Cell Sci. 83, 313–340 (1986)

    Google Scholar 

  • E.L. Elson, Cellular mechanics as an indicator of cytoskeletal structure and function Annu. Rev. Biophys. Biophys. Chem. 17, 397–430 (1988), doi:10.1146/annurev.bb.17.060188.002145

    Article  Google Scholar 

  • S.M. Emani, M.J. Ellis, L.R. Dibernardo, S. Colgrove, D.D. Glower, D.A. Taylor, Systolic contraction within aneurysmal rabbit myocardium following transplantation of autologous skeletal myoblasts J. Surg. Res. 135, 202–208 (2006), doi:10.1016/j.jss.2006.03.020

    Article  Google Scholar 

  • N. Endlich, K. Endlich, Stretch, tension and adhesion—adaptive mechanisms of the actin cytoskeleton in podocytes Eur. J. Cell Biol. 85, 229–234 (2006), doi:10.1016/j.ejcb.2005.09.006

    Article  Google Scholar 

  • J. Engel, J. Chen, N. Chen, S. Pandya, C. Liu, Development and characterization of an artificial hair cell based on polyurethane elastomer and force sensitive resistors. In Proceedings of the 4th IEEE International Conference on Sensors, Irvine, Calif, USA (2005)

  • M.A. Gaballa, T.E. Raya, B.R. Simon, S. Goldman, Arterial mechanics in spontaneously hypertensive rats. Mechanical properties, hydraulic conductivity, and two-phase (solid/fluid) finite element models Circ. Res. 71, 145–158 (1992)

    Google Scholar 

  • J.A. Gilbert, P.S. Weinhold, A.J. Banes, G.W. Link, G.L. Jones, Strain profiles for circular cell culture plates containing flexible surfaces employed to mechanically deform cells in vitro J. Biomech. 27, 1169–1177 (1994), doi:10.1016/0021-9290(94)90057-4

    Article  Google Scholar 

  • S.M. Gopalan, C. Flaim, S.N. Bhatia, M. Hoshijima, R. Knoell, K.R. Chien et al., Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers Biotechnol. Bioeng. 81, 578–587 (2003), doi:10.1002/bit.10506

    Article  Google Scholar 

  • F. Guilak, A. Ratcliffe, V.C. Mow, Chondrocyte deformation and local tissue strain in articular cartilage: a confocal microscopy study J. Orthop. Res. 13, 410–421 (1995), doi:10.1002/jor.1100130315

    Article  Google Scholar 

  • J.H. Haga, Y.S. Li, S. Chien, Molecular basis of the effects of mechanical stretch on vascular smooth muscle cells J. Biomech. 40, 947–960 (2007), doi:10.1016/j.jbiomech.2006.04.011

    Article  Google Scholar 

  • H. Hirata, H. Tatsumi, M. Sokabe, Dynamics of actin filaments during tension-dependent formation of actin bundles Biochim. Biophys. Acta 1770, 1115–1127 (2007)

    Google Scholar 

  • D.E. Ingber, Mechanical signaling and the cellular response to extracellular matrix in angiogenesis and cardiovascular physiology Circ. Res. 91, 877–887 (2002), doi:10.1161/01.RES.0000039537.73816.E5

    Article  Google Scholar 

  • D.E. Ingber, Tensegrity II. How structural networks influence cellular information processing networks J. Cell Sci. 116, 1397–1408 (2003a), doi:10.1242/jcs.00360

    Article  Google Scholar 

  • D.E. Ingber, Tensegrity I. Cell structure and hierarchical systems biology J. Cell Sci. 116, 1157–1173 (2003b), doi:10.1242/jcs.00359

    Article  Google Scholar 

  • F. Ishida, H. Ogawa, T. Simizu, T. Kojima, W. Taki, Visualizing the dynamics of cerebral aneurysms with four-dimensional computed tomographic angiography Neurosurgery 57, 460–471 (2005)discussion 460–471, doi:10.1227/01.NEU.0000170540.17300.DD

    Article  Google Scholar 

  • B.F. Jones, M.E. Wall, R.L. Carroll, S. Washburn, A.J. Banes, Ligament cells stretch-adapted on a microgrooved substrate increase intercellular communication in response to a mechanical stimulus J. Biomech. 38, 1653–1664 (2005), doi:10.1016/j.jbiomech.2004.07.027

    Article  Google Scholar 

  • H. Kenar, G.T. Kose, V. Hasirci, Tissue engineering of bone on micropatterned biodegradable polyester films Biomaterials 27, 885–895 (2006), doi:10.1016/j.biomaterials.2005.07.001

    Article  Google Scholar 

  • T. Kozai, M. Eto, Z. Yang, H. Shimokawa, T.F. Luscher, Statins prevent pulsatile stretch-induced proliferation of human saphenous vein smooth muscle cells via inhibition of Rho/Rho-kinase pathway Cardiovasc. Res. 68, 475–482 (2005), doi:10.1016/j.cardiores.2005.07.002

    Article  Google Scholar 

  • K. Kurpinski, J. Chu, C. Hashi, S. Li, Anisotropic mechanosensing by mesenchymal stem cells Proc. Natl. Acad. Sci. USA 103, 16095–16100 (2006a), doi:10.1073/pnas.0604182103

    Article  Google Scholar 

  • K. Kurpinski, J. Park, R.G. Thakar, S. Li, Regulation of vascular smooth muscle cells and mesenchymal stem cells by mechanical strain Mol. Cell. Biomech. 3, 21–34 (2006b)

    Google Scholar 

  • J.S. Lee, C.M. Hale, P. Panorchan, S.B. Khatau, J.P. George, Y. Tseng et al., Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration Biophys. J. 93, 2542–2552 (2007), doi:10.1529/biophysj.106.102426

    Article  Google Scholar 

  • S. Lehoux, A. Tedgui, Cellular mechanics and gene expression in blood vessels J. Biomech. 36, 631–643 (2003), doi:10.1016/S0021-9290(02)00441-4

    Article  Google Scholar 

  • Q. Li, Y. Muragaki, H. Ueno, A. Ooshima, Stretch-induced proliferation of cultured vascular smooth muscle cells and a possible involvement of local renin–angiotensin system and platelet-derived growth factor (PDGF) Hypertens. Res. 20, 217–223 (1997), doi:10.1291/hypres.20.217

    Article  Google Scholar 

  • G.S. Lin, H.H. Hines, G. Grant, K. Taylor, C. Ryals, Automated quantification of myocardial ischemia and wall motion defects by use of cardiac SPECT polar mapping and 4-dimensional surface rendering J. Nucl. Med. Technol. 34, 3–17 (2006)

    Google Scholar 

  • W. Lötters, J.C. Olthuis, P.H. Veltink, P. Bergveld, The mechanical properties of the rubber elastic polymer polydimethylsiloxane for sensor applications J. Micromech. Microeng. 7, 145–147 (1997). doi:10.1088/0960-1317/7/3/017

    Article  Google Scholar 

  • G.N. Maksym, L. Deng, N.J. Fairbank, C.A. Lall, S.C. Connolly, Beneficial and harmful effects of oscillatory mechanical strain on airway smooth muscle Can. J. Physiol. Pharmacol. 83, 913–922 (2005), doi:10.1139/y05-091

    Article  Google Scholar 

  • M. Malina, T. Lanne, K. Ivancev, B. Lindblad, J. Brunkwall, Reduced pulsatile wall motion of abdominal aortic aneurysms after endovascular repair J. Vasc. Surg. 27, 624–631 (1998), doi:10.1016/S0741-5214(98)70226-5

    Article  Google Scholar 

  • I.V. Maly, R.T. Lee, D.A. Lauffenburger, A model for mechanotransduction in cardiac muscle: effects of extracellular matrix deformation on autocrine signaling Ann. Biomed. Eng. 32, 1319–1335 (2004), doi:10.1114/B:ABME.0000042221.61633.23

    Article  Google Scholar 

  • A.J. Maniotis, C.S. Chen, D.E. Ingber, Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure Proc. Natl. Acad. Sci. USA 94, 849–854 (1997), doi:10.1073/pnas.94.3.849

    Article  Google Scholar 

  • N.L. McKnight, J.A. Frangos, Strain rate mechanotransduction in aligned human vascular smooth muscle cells Ann. Biomed. Eng. 31, 239–249 (2003), doi:10.1114/1.1543935

    Article  Google Scholar 

  • M. Moretti, A. Prina-Mello, A.J. Reid, V. Barron, P.J. Prendergast, Endothelial cell alignment on cyclically-stretched silicone surfaces J. Mater. Sci. Mater. Med. 15, 1159–1164 (2004), doi:10.1023/B:JMSM.0000046400.18607.72

    Article  Google Scholar 

  • D. Morrow, C. Sweeney, Y.A. Birney, S. Guha, N. Collins, P.M. Cummins et al., Biomechanical regulation of hedgehog signaling in vascular smooth muscle cells in vitro and in vivo Am. J. Physiol. Cell Physiol. 292, C488–C496 (2007), doi:10.1152/ajpcell.00337.2005

    Article  Google Scholar 

  • A. Nicolas, B. Geiger, S.A. Safran, Cell mechanosensitivity controls the anisotropy of focal adhesions Proc. Natl. Acad. Sci. USA 101, 12520–12525 (2004), doi:10.1073/pnas.0403539101

    Article  Google Scholar 

  • J.D. Pajerowski, K.N. Dahl, F.L. Zhong, P.J. Sammak, D.E. Discher, Physical plasticity of the nucleus in stem cell differentiation Proc. Natl. Acad. Sci. USA 104, 15619–15624 (2007), doi:10.1073/pnas.0702576104

    Article  Google Scholar 

  • J.S. Park, J.S. Chu, C. Cheng, F. Chen, D. Chen, S. Li, Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells Biotechnol. Bioeng. 88, 359–368 (2004), doi:10.1002/bit.20250

    Article  Google Scholar 

  • E.A. Peeters, C.V. Bouten, C.W. Oomens, D.L. Bader, L.H. Snoeckx, F.P. Baaijens, Anisotropic, three-dimensional deformation of single attached cells under compression Ann. Biomed. Eng. 32, 1443–1452 (2004), doi:10.1114/B:ABME.0000042231.59230.72

    Article  Google Scholar 

  • E.N. Pugacheva, F. Roegiers, E.A. Golemis, Interdependence of cell attachment and cell cycle signaling Curr. Opin. Cell Biol. 18, 507–515 (2006), doi:10.1016/j.ceb.2006.08.014

    Article  Google Scholar 

  • M.N. Richard, J.F. Deniset, A.L. Kneesh, D. Blackwood, G.N. Pierce, Mechanical stretching stimulates smooth muscle cell growth, nuclear protein import, and nuclear pore expression through mitogen-activated protein kinase activation J. Biol. Chem. 282, 23081–23088 (2007), doi:10.1074/jbc.M703602200

    Article  Google Scholar 

  • G.M. Riha, P.H. Lin, A.B. Lumsden, Q. Yao, C. Chen, Roles of hemodynamic forces in vascular cell differentiation Ann. Biomed. Eng. 33, 772–779 (2005), doi:10.1007/s10439-005-3310-9

    Article  Google Scholar 

  • S. Sarkar, M. Dadhania, P. Rourke, T.A. Desai, J.Y. Wong, Vascular tissue engineering: microtextured scaffold templates to control organization of vascular smooth muscle cells and extracellular matrix Acta Biomater. 1, 93–100 (2005), doi:10.1016/j.actbio.2004.08.003

    Article  Google Scholar 

  • M. Thery, M. Bornens, Cell shape and cell division Curr. Opin. Cell Biol. 18, 648–657 (2006), doi:10.1016/j.ceb.2006.10.001

    Article  Google Scholar 

  • K. Van Vliet, G. Bao, S. Suresh, The biomechanics toolbox: experimental approaches for living cells and biomolecules Acta Mater. 51, 5881–5905 (2003). doi:10.1016/j.actamat.2003.09.001

    Article  Google Scholar 

  • J.H. Wang, E.S. Grood, The strain magnitude and contact guidance determine orientation response of fibroblasts to cyclic substrate strains Connect. Tissue Res. 41, 29–36 (2000), doi:10.3109/03008200009005639

    Article  Google Scholar 

  • J.H. Wang, G. Yang, Z. Li, W. Shen, Fibroblast responses to cyclic mechanical stretching depend on cell orientation to the stretching direction J. Biomech. 37, 573–576 (2004), doi:10.1016/j.jbiomech.2003.09.011

    Article  Google Scholar 

  • Y. Zhang, J. Takagawa, R.E. Sievers, M.F. Khan, M.N. Viswanathan, M.L. Springer et al., Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction Am. J. Physiol. Heart Circ. Physiol. 292, H1187–H1192 (2007), doi:10.1152/ajpheart.00895.2006

    Article  Google Scholar 

  • C. Zhu, G. Bao, N. Wang, Cell mechanics: mechanical response, cell adhesion, and molecular deformation Annu. Rev. Biomed. Eng. 2, 189–226 (2000), doi:10.1146/annurev.bioeng.2.1.189

    Article  Google Scholar 

Download references

Acknowledgements

This work was partially supported by a Seed grant from the University of Colorado and Postle Fund from the Children’s Hospital. We would like to thank Aaron Richman, Lunghao Hu, Vadim Tsvinskin and Christopher Rockne for their help in the study.

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, University of Colorado at Boulder, Boulder, CO, 80309, USA

    Wei Tan, Devon Scott, Dmitry Belchenko, H. Jerry Qi & Long Xiao

  2. Department of Pediatrics, University of Colorado Health Science Center, Denver, CO, 80262, USA

    Wei Tan

Authors
  1. Wei Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Devon Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dmitry Belchenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Jerry Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Long Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Tan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, W., Scott, D., Belchenko, D. et al. Development and evaluation of microdevices for studying anisotropic biaxial cyclic stretch on cells. Biomed Microdevices 10, 869–882 (2008). https://doi.org/10.1007/s10544-008-9201-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-008-9201-8

Keywords

Search

Navigation