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Microactuator device for integrated measurement of epithelium mechanics

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Abstract

Mechanical forces are among important factors that drive cellular function and organization. We present a microfabricated device with on-chip actuation for mechanical testing of single cells. An integrated immersible electrostatic actuator system is demonstrated that applies calibrated forces to cells. We conduct stretching experiments by directly applying forces to epithelial cells adhered to device surfaces functionalized with collagen. We measure mechanical properties including stiffness, hysteresis and visco-elasticity of adherent cells.

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References

  • D. Mizuno, C. Tardin, C.F. Schmidt, F.C. MacKintosh, Nonequilibrium mechanics of active cytoskeletal networks. Science 315(5810), 370–373 (2007)

    Article  Google Scholar 

  • D.E. Ingber, Mechanobiology and diseases of mechanotransduction. Ann. Med. 35(8), 564–577 (2003)

    Article  Google Scholar 

  • S. Suresh, J. Spatz, J.P. Mills, A. Micoulet, M. Dao, C.T. Lim, M. Beil, T. Seufferlein, Connections between single-cell biomechanics and human disease states: gastrointestinal cancer and malaria. Acta Biomater. 1(1), 15–30 (2005)

    Article  Google Scholar 

  • R.M. Hocumuth, Micropipette aspiration of living cells. J. Biomech. 33(1), 15–22 (2000)

    Article  Google Scholar 

  • M. Frisen, M. Magi, L. Sonnerup, A. Viidik, Rheological analysis of soft collagenous tissue. part ii: experimental evaluations and verifications. J. Biomech. 2(1), 21–8 (1969)

    Article  Google Scholar 

  • P.A. Janmey, D.A. Weitz, Dealing with mechanics: mechanisms of force transduction in cells. Trends Biochem. Sci. 29(7), 364–370 (2004)

    Article  Google Scholar 

  • N. Wang, J.P. Butler, D.E. Ingber, Mechanotransduction across cell surface through cytoskeleton. Science 260(5111), 1124–1127 (1993)

    Article  Google Scholar 

  • R.E. Mahaffy, S. Park, E. Gerde, J. Ka, C.K. Shih, Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy. Biophys. J. 86, 1777–17793 (2004)

    Article  Google Scholar 

  • M.T.A. Saif, C.R. Sager, S. Coyer, Functionalized biomicroelectromechanical systems sensors for force response study at local adhesion sites of single livling cells on substrates. Ann. Biomed. Eng. 31, 950–961 (2003)

    Article  Google Scholar 

  • J. Rajagopalan, A. Tofangchi, M.T.A. Saif, Drosophila neurons actively regulate axonal tension in vivo. Biophys. J. 99(10), 3208–3215 (2010)

    Article  Google Scholar 

  • O. Thoumine, A. Ott, Time scale dependent viscoelastic and contractile regimes in fibroblasts probed by microplate manipulation. J. Cell Sci. 110(17), 2109–2116 (1997)

    Google Scholar 

  • A. Micoulet, J.P. Spatz, A. Ott, Mechanical response analysis and power generation by single-cell stretching. ChemPhysChem 6(4), 663–670 (2005)

    Article  Google Scholar 

  • N. Desprat, A. Richert, J. Simeon, A. Asnacios, Creep function of a single living cell. Biophys. J. 88(3), 2224–2233 (2005)

    Article  Google Scholar 

  • G. Bao, S. Suresh, Cell and molecular mechanics of biological materials. Nat. Mater. 2, 715–725 (2003)

    Article  Google Scholar 

  • K.J.V. Vliet, G. Bao, S. Suresh, The biomechanics toolbox: experimental approaches for living cells and biomolecules. Acta Mater. 51, 5881–5905 (2003)

    Article  Google Scholar 

  • O. Loh, A. Vaziri, H. Espinosa, The potential of MEMS for advancing experiments and modeling in cell mechanics. Exp. Mech. 49(1), 105–124 (2009)

    Article  Google Scholar 

  • J. Rajagopalan, M.T.A. Saif, MEMS sensors and microsystems for cell mechanobiology. J. Micromechanics Microengineering 21(5), 054002 (2011)

    Article  Google Scholar 

  • D.B. Serrell, T.L. Oreskovic, A.J. Slifka, R.L. Mahajan, D.S. Finch, A uniaxial biomems device for quantitative force-displacement measurements. Biomed. Microdevices 9(2), 267–275 (2007)

    Article  Google Scholar 

  • D.B. Serrell, J. Law, A.J. Slifka, R.L. Mahajan, D.S. Finch, A uniaxial biomems device for imaging single cell response during quantitative force-displacement measurements. Biomed. Microdevices 10(6), 883–889 (2008)

    Article  Google Scholar 

  • M.E. Chicurel, C.S. Chen, D.E. Ingber, Cellular control lies in the balance of forces. Curr. Opin. Cell Biol. 10, 232–239 (1998)

    Article  Google Scholar 

  • N.Q. Balaban, U.S. Schwarz, D. Riveline, P. Goichberg, G. Tzur, I. Sabanay, D. Mahalu, S. Safran, A. Bershadsky, L. Addadi, B. Geiger, Force and focal adhesion assebly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3, 466–427 (2001)

    Article  Google Scholar 

  • N. Chronis, L.P. Lee, Electrothermally activated su-8 microgripper for single cell manipulation in solution. J. Microeletromech. Sys. 14(4), 857–863 (2005)

    Article  Google Scholar 

  • Y. Sun, K.-T. Wan, K.P. Roberts, J.C. Bischof, B.J. Nelson, Mechanical property characterization of mouse zona pellucida. IEEE Trans. NanoBioSci. 2(4), 279–286 (2003)

    Article  Google Scholar 

  • Y. Sun, B. Nelson, M.A. Greminger, Investigating protein structure change in the zona pellucida with a microrobotic system. Int. J. Rob. Res. 24(2–3), 211–208 (2004)

    Google Scholar 

  • T.L. Sounart, T.A. Michalske, K.R. Zavadil, Frequency-dependent electrostatic actuation in microfluidic mems. J. Microeletromech. Sys. 14(1), 125–133 (2005)

    Article  Google Scholar 

  • V. Mukundan, B.L. Pruitt, Mems electrostatic actuation in conducting biological media. J. Microeletromech. Sys. 18(2), 405–413 (2009)

    Article  Google Scholar 

  • C. Brunner, A. Niendorf, J.A. Kas, Passive and active single-cell biomechanics: a new perspective in cancer diagnosis. Soft Matter 5, 2171–2178 (2009)

    Article  Google Scholar 

  • V. Mukundan, P. Ponce, H.E. Butterfield, B.L. Pruitt, Modeling and characterization of electrostatic comb-drive actuators in conducting liquid media. J. Micromechanics Microengineering 19(065008), 9 (2009)

    Google Scholar 

  • R. Legtenberg, A.W. Groeneveld, M. Elwenspoek, Comb-drive actuators for large displacements. J. Micromechanics Microengineering 6, 320–329 (1996)

    Article  Google Scholar 

  • N.A. Burnham, X. Chen, C.S. Hodges, G.A. Matei, E.J. Thoreson, C.J. Roberts, M.C. Davies, S.J.B. Tendler, Comparison of calibration methods for atomic-force microscopy cantilevers. Nanotechnology 14, 1–6 (2003)

    Article  Google Scholar 

  • P. Fernandez, A. Ott, Single cell mechanics: stress stiffening and kinematic hardening. Phys. Rev. Lett. 100(23), 238102 (2008)

    Article  Google Scholar 

  • Y.C. Fung, Biomechanics: Mechanical Properties of Living Tissues. Springer, New York (1993)

    Google Scholar 

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Acknowledgements

This work is supported by NSF CAREER award ECS0449499, NIH R01EB006745-01A1 and NSF EFRI (MIKS-1136790). Fabrication was done at the Stanford Nanofabrication Facility, which is supported by NSF under grant ECS 9731293. VM was supported by the Stanford Graduate Fellowship. WJN is supported by National Institutes of Health grant GM35527.

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Correspondence to Beth L. Pruitt.

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Mukundan, V., Nelson, W.J. & Pruitt, B.L. Microactuator device for integrated measurement of epithelium mechanics. Biomed Microdevices 15, 117–123 (2013). https://doi.org/10.1007/s10544-012-9693-0

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  • DOI: https://doi.org/10.1007/s10544-012-9693-0

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