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Measuring cell-generated forces: a guide to the available tools

Abstract

Forces generated by cells are critical regulators of cell adhesion, signaling, and function, and they are also essential drivers in the morphogenetic events of development. Over the past 20 years, several methods have been developed to measure these forces. However, despite recent substantial interest in understanding the contribution of these forces in biology, implementation and adoption of the developed methods by the broader biological community remain challenging because of the inherently multidisciplinary expertise required to conduct and interpret the measurements. In this review, we introduce the established methods and highlight the technical challenges associated with implementing each technique in a biological laboratory.

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Figure 1: ECM mechanical properties determine the relationship between force and deformation.
Figure 2: Methods for measuring cellular forces.
Figure 3: Cellular tractions on 2D and in 3D substrates.

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References

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

    Article  CAS  PubMed  Google Scholar 

  2. Bell, E., Ivarsson, B. & Merrill, C. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci. USA 76, 1274–1278 (1979).This study presents early observations of collagen hydrogel contraction as a measure of cell contractility.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ehrlich, H.P. & Rajaratnam, J.B.M. Cell locomotion forces versus cell contraction forces for collagen lattice contraction: an in vitro model of wound contraction. Tissue Cell 22, 407–417 (1990).

    Article  CAS  PubMed  Google Scholar 

  4. Dallon, J.C. & Ehrlich, H.P. A review of fibroblast-populated collagen lattices. Wound Repair Regen. 16, 472–479 (2008).

    Article  PubMed  Google Scholar 

  5. Stopak, D. & Harris, A.K. Connective tissue morphogenesis by fibroblast traction. Dev. Biol. 90, 383–398 (1982).

    Article  CAS  PubMed  Google Scholar 

  6. Ngo, P., Ramalingam, P., Phillips, J.A. & Furuta, G.T. in Cell-Cell Interactions Vol. 341 (ed. Colgan, S.P.) 103–109 (Humana Press, 2006).

  7. Smith, K.D., Wells, A. & Lauffenburger, D.A. Multiple signaling pathways mediate compaction of collagen matrices by EGF-stimulated fibroblasts. Exp. Cell Res. 312, 1970–1982 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Fernandez-Gonzalez, R. et al. Dynamics are regulated by tension in intercalating cells. Dev. Cell 17, 736–743 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fernandez-Gonzalez, R. & Zallen, J.A. Wounded cells drive rapid epidermal repair in the early Drosophila embryo. Mol. Biol. Cell 24, 3227–3237 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Farhadifar, R., Röper, J.-C., Aigouy, B., Eaton, S. & Jülicher, F. The influence of cell mechanics, cell-cell interactions, and proliferation on epithelial packing. Curr. Biol. 17, 2095–2104 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Delvoye, P., Wiliquet, P., Leveque, J.-L., Nusgens, B.V. & Lapiere, C.M. Measurement of mechanical forces generated by skin fibroblasts embedded in a three-dimensional collagen gel. J. Invest. Dermatol. 97, 898–902 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Zimmermann, W.H. et al. Three-dimensional engineered heart tissue from neonatal rat cardiac myocytes. Biotechnol. Bioeng. 68, 106–114 (2000).This study combined the use of tissue contraction and cantilevers to assemble engineered tissues and allow force measurement.

    Article  CAS  PubMed  Google Scholar 

  13. Dennis, R.G. & Kosnik, P.E. Excitability and isometric contractile properties of mammalian skeletal muscle constructs engineered in vitro. In Vitro Cell. Dev. Biol. Anim. 36, 327–335 (2000).

    Article  CAS  PubMed  Google Scholar 

  14. Vandenburgh, H. et al. Automated drug screening with contractile muscle tissue engineered from dystrophic myoblasts. FASEB J. 23, 3325–3334 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Vandenburgh, H. et al. Drug-screening platform based on the contractility of tissue-engineered muscle. Muscle Nerve 37, 438–447 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Hansen, A. et al. Development of a drug screening platform based on engineered heart tissue. Circ. Res. 107, 35–44 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. Zimmermann, W.-H. Tissue engineering of a differentiated cardiac muscle construct. Circ. Res. 90, 223–230 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Legant, W.R. et al. Microfabricated tissue gauges to measure and manipulate forces from 3D microtissues. Proc. Natl. Acad. Sci. USA 106, 10097–10102 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Serrao, G.W. et al. Myocyte-depleted engineered cardiac tissues support therapeutic potential of mesenchymal stem cells. Tissue Eng. Part A 18, 1322–1333 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Boudou, T. et al. A microfabricated platform to measure and manipulate the mechanics of engineered cardiac microtissues. Tissue Eng. Part A 18, 910–919 (2012).

    Article  CAS  PubMed  Google Scholar 

  21. Sakar, M.S. et al. Formation and optogenetic control of engineered 3D skeletal muscle bioactuators. Lab Chip 12, 4976–4985 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hinson, J.T. et al. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy. Science 349, 982–986 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Whitesides, G.M., Ostuni, E., Takayama, S., Jiang, X. & Ingber, D.E. Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3, 335–373 (2001).

    Article  CAS  PubMed  Google Scholar 

  24. Bower, A.F. Applied Mechanics of Solids (CRC Press, 2009).

  25. Harris, A.K., Wild, P. & Stopak, D. Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208, 177–179 (1980).A seminal demonstration of the use of synthetic materials to observe cellular forces.

    Article  CAS  PubMed  Google Scholar 

  26. Harris, A.K., Stopak, D. & Wild, P. Fibroblast traction as a mechanism for collagen morphogenesis. Nature 290, 249–251 (1981).

    Article  CAS  PubMed  Google Scholar 

  27. Lee, J. Traction forces generated by locomoting keratocytes. J. Cell Biol. 127, 1957–1964 (1994).

    Article  CAS  PubMed  Google Scholar 

  28. Dembo, M., Oliver, T., Ishihara, A. & Jacobson, K. Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys. J. 70, 2008–2022 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Legant, W.R. et al. Multidimensional traction force microscopy reveals out-of-plane rotational moments about focal adhesions. Proc. Natl. Acad. Sci. USA 110, 881–886 (2013).

    Article  CAS  PubMed  Google Scholar 

  30. Hur, S.S., Zhao, Y., Li, Y.-S., Botvinick, E. & Chien, S. Live cells exert 3-dimensional traction forces on their substrata. Cell. Mol. Bioeng. 2, 425–436 (2009).

    Article  PubMed  Google Scholar 

  31. Maskarinec, S.A., Franck, C., Tirrell, D.A. & Ravichandran, G. Quantifying cellular traction forces in three dimensions. Proc. Natl. Acad. Sci. USA 106, 22108–22113 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Balaban, N.Q. et al. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3, 466–472 (2001).The authors implement a TFM method to investigate the relationship between cell traction forces and the molecular structure of cell adhesions.

    Article  CAS  PubMed  Google Scholar 

  33. Beningo, K.A., Dembo, M., Kaverina, I., Small, J.V. & Wang, Y.L. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153, 881–888 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Dembo, M. & Wang, Y.-L. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys. J. 76, 2307–2316 (1999).An important study that used TFM to characterize the forces generated by migrating fibroblasts.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Jannat, R.A., Dembo, M. & Hammer, D.A. Traction forces of neutrophils migrating on compliant substrates. Biophys. J. 101, 575–584 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Plotnikov, S.V., Pasapera, A.M., Sabass, B. & Waterman, C.M. Force fluctuations within focal adhesions mediate ECM-rigidity sensing to guide directed cell migration. Cell 151, 1513–1527 (2012).The authors use high-resolution TFM to characterize the distribution of forces within single focal adhesions.

    Article  CAS  PubMed  Google Scholar 

  37. Engler, A.J., Sen, S., Sweeney, H.L. & Discher, D.E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Kraning-Rush, C.M., Califano, J.P. & Reinhart-King, C.A. Cellular traction stresses increase with increasing metastatic potential. PLoS ONE 7, e32572 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Oliver, T., Jacobson, K. & Dembo, M. Design and use of substrata to measure traction forces exerted by cultured cells. Methods Enzymol. 298, 497–521 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Beningo, K.A. & Wang, Y.-L. Flexible substrata for the detection of cellular traction forces. Trends Cell Biol. 12, 79–84 (2002).

    Article  CAS  PubMed  Google Scholar 

  41. Khetan, S. et al. Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels. Nat. Mater. 12, 458–465 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kim, I.L., Khetan, S., Baker, B.M., Chen, C.S. & Burdick, J.A. Fibrous hyaluronic acid hydrogels that direct MSC chondrogenesis through mechanical and adhesive cues. Biomaterials 34, 5571–5580 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hall, M.S. et al. Toward single cell traction microscopy within 3D collagen matrices. Exp. Cell Res. 319, 2396–2408 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Style, R.W. et al. Traction force microscopy in physics and biology. Soft Matter 10, 4047 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. Wang, J.H.-C. & Lin, J.-S. Cell traction force and measurement methods. Biomech. Model. Mechanobiol. 6, 361–371 (2007).

    Article  PubMed  Google Scholar 

  46. Tseng, Q. et al. Spatial organization of the extracellular matrix regulates cell-cell junction positioning. Proc. Natl. Acad. Sci. USA 109, 1506–1511 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Schwarz, U.S. et al. Calculation of forces at focal adhesions from elastic substrate data: the effect of localized force and the need for regularization. Biophys. J. 83, 1380–1394 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hur, S.S. et al. Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells. Proc. Natl. Acad. Sci. USA 109, 11110–11115 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sabass, B., Gardel, M.L., Waterman, C.M. & Schwarz, U.S. High resolution traction force microscopy based on experimental and computational advances. Biophys. J. 94, 207–220 (2008).

    Article  CAS  PubMed  Google Scholar 

  50. Franck, C., Hong, S., Maskarinec, S.A., Tirrell, D.A. & Ravichandran, G. Three-dimensional full-field measurements of large deformations in soft materials using confocal microscopy and digital volume correlation. Exp. Mech. 47, 427–438 (2007).

    Article  Google Scholar 

  51. Franck, C., Maskarinec, S.A., Tirrell, D.A. & Ravichandran, G. Three-dimensional traction force microscopy: a new tool for quantifying cell-matrix interactions. PLoS ONE 6, e17833 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. del Álamo, J.C. et al. Three-dimensional quantification of cellular traction forces and mechanosensing of thin substrata by Fourier traction force microscopy. PLoS ONE 8, e69850 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Baker, B.M. & Chen, C.S. Deconstructing the third dimension—how 3D culture microenvironments alter cellular cues. J. Cell Sci. 125, 3015–3024 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Koch, T.M., Münster, S., Bonakdar, N., Butler, J. & Fabry, B. III Traction forces in cancer cell invasion. PLoS ONE 7, e33476 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Bloom, R.J., George, J.P., Celedon, A., Sun, S.X. & Wirtz, D. Mapping local matrix remodeling induced by a migrating tumor cell using three-dimensional multiple-particle tracking. Biophys. J. 95, 4077–4088 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Steinwachs, J. et al. Three-dimensional force microscopy of cells in biopolymer networks. Nat. Methods 13, 171–176 (2016).

    Article  CAS  PubMed  Google Scholar 

  57. Legant, W.R. et al. Measurement of mechanical tractions exerted by cells in three-dimensional matrices. Nat. Methods 7, 969–971 (2010).This study characterized the traction stresses generated by cells embedded in 3D PEG hydrogels.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Galbraith, C.G. & Sheetz, M.P. A micromachined device provides a new bend on fibroblast traction forces. Proc. Natl. Acad. Sci. USA 94, 9114–9118 (1997).An example of a packaged microfabricated platform designed to measure cellular forces in real time.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rajagopalan, J., Tofangchi, A. & Saif, M.T.A. Linear high-resolution BioMEMS force sensors with large measurement range. J. Microelectromech. Syst. 19, 1380–1389 (2010).

    Article  CAS  Google Scholar 

  60. Rajagopalan, J. & Saif, M.T.A. MEMS sensors and microsystems for cell mechanobiology. J. Micromech. Microeng. 21, 54002 (2011).

    Article  PubMed  Google Scholar 

  61. Park, J. et al. Real-time measurement of the contractile forces of self-organized cardiomyocytes on hybrid biopolymer microcantilevers. Anal. Chem. 77, 6571–6580 (2005).

    Article  CAS  PubMed  Google Scholar 

  62. Feinberg, A.W. et al. Muscular thin films for building actuators and powering devices. Science 317, 1366–1370 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Grosberg, A., Alford, P.W., McCain, M.L. & Parker, K.K. Ensembles of engineered cardiac tissues for physiological and pharmacological study: heart on a chip. Lab Chip 11, 4165 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Bhatia, S.N. & Ingber, D.E. Microfluidic organs-on-chips. Nat. Biotechnol. 32, 760–772 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Huh, D., Hamilton, G.A. & Ingber, D.E. From 3D cell culture to organs-on-chips. Trends Cell Biol. 21, 745–754 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tan, J.L. et al. Cells lying on a bed of microneedles: an approach to isolate mechanical force. Proc. Natl. Acad. Sci. USA 100, 1484–1489 (2003).An early report of micropillar arrays used to measure the forces generated by cells as a function of substrate stiffness and cell shape.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Fu, J. et al. Mechanical regulation of cell function with geometrically modulated elastomeric substrates. Nat. Methods 7, 733–736 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Trichet, L. et al. Evidence of a large-scale mechanosensing mechanism for cellular adaptation to substrate stiffness. Proc. Natl. Acad. Sci. USA 109, 6933–6938 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. du Roure, O. et al. Force mapping in epithelial cell migration. Proc. Natl. Acad. Sci. USA 102, 2390–2395 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Ganz, A. et al. Traction forces exerted through N-cadherin contacts. Biol. Cell 98, 721–730 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Liu, Z. et al. Mechanical tugging force regulates the size of cell-cell junctions. Proc. Natl. Acad. Sci. USA 107, 9944–9949 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Maruthamuthu, V., Sabass, B., Schwarz, U.S. & Gardel, M.L. Cell-ECM traction force modulates endogenous tension at cell-cell contacts. Proc. Natl. Acad. Sci. USA 108, 4708–4713 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Saez, A., Ghibaudo, M., Buguin, A., Silberzan, P. & Ladoux, B. Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates. Proc. Natl. Acad. Sci. USA 104, 8281–8286 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Ghassemi, S. et al. Cells test substrate rigidity by local contractions on submicrometer pillars. Proc. Natl. Acad. Sci. USA 109, 5328–5333 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Yang, M.T., Fu, J., Wang, Y.-K., Desai, R.A. & Chen, C.S. Assaying stem cell mechanobiology on microfabricated elastomeric substrates with geometrically modulated rigidity. Nat. Protoc. 6, 187–213 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Stabley, D.R., Jurchenko, C., Marshall, S.S. & Salaita, K.S. Visualizing mechanical tension across membrane receptors with a fluorescent sensor. Nat. Methods 9, 64–67 (2011).

    Article  PubMed  CAS  Google Scholar 

  77. Liu, Y., Yehl, K., Narui, Y. & Salaita, K. Tension sensing nanoparticles for mechano-imaging at the living/nonliving interface. J. Am. Chem. Soc. 135, 5320–5323 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Morimatsu, M., Mekhdjian, A.H., Adhikari, A.S. & Dunn, A.R. Molecular tension sensors report forces generated by single integrin molecules in living cells. Nano Lett. 13, 3985–3989 (2013).

    Article  CAS  PubMed  Google Scholar 

  79. Liu, Y. et al. Nanoparticle tension probes patterned at the nanoscale: impact of integrin clustering on force transmission. Nano Lett. 14, 5539–5546 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Wang, X. & Ha, T. Defining single molecular forces required to activate integrin and Notch signaling. Science 340, 991–994 (2013).The authors implemented DNA-based sensors to measure the forces applied to single integrin molecules during early adhesion.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Blakely, B.L. et al. A DNA-based molecular probe for optically reporting cellular traction forces. Nat. Methods 11, 1229–1232 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhang, Y., Ge, C., Zhu, C. & Salaita, K. DNA-based digital tension probes reveal integrin forces during early cell adhesion. Nat. Commun. 5, 5167 (2014).

    Article  CAS  PubMed  Google Scholar 

  83. Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263–266 (2010).A seminal study in which an engineered cell-adhesion protein is used to measure the forces in focal adhesions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Hoffman, B.D., Grashoff, C. & Schwartz, M.A. Dynamic molecular processes mediate cellular mechanotransduction. Nature 475, 316–323 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Conway, D.E. et al. Fluid shear stress on endothelial cells modulates mechanical tension across VE-cadherin and PECAM-1. Curr. Biol. 23, 1024–1030 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Borghi, N. et al. E-cadherin is under constitutive actomyosin-generated tension that is increased at cell-cell contacts upon externally applied stretch. Proc. Natl. Acad. Sci. USA 109, 12568–12573 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Meng, F. & Sachs, F. Visualizing dynamic cytoplasmic forces with a compliance-matched FRET sensor. J. Cell Sci. 124, 261–269 (2011).

    Article  CAS  PubMed  Google Scholar 

  88. Smith, M.L. et al. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLoS Biol. 5, e268 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Cost, A.-L., Ringer, P., Chrostek-Grashoff, A. & Grashoff, C. How to measure molecular forces in cells: a guide to evaluating genetically-encoded FRET-based tension sensors. Cell. Mol. Bioeng. 8, 96–105 (2015).

    Article  CAS  PubMed  Google Scholar 

  90. Mammoto, T. & Ingber, D.E. Mechanical control of tissue and organ development. Development 137, 1407–1420 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Campàs, O. et al. Quantifying cell-generated mechanical forces within living embryonic tissues. Nat. Methods 11, 183–189 (2014).

    Article  PubMed  CAS  Google Scholar 

  92. Paszek, M.J. et al. Tensional homeostasis and the malignant phenotype. Cancer Cell 8, 241–254 (2005).

    Article  CAS  PubMed  Google Scholar 

  93. McBeath, R., Pirone, D.M., Nelson, C.M., Bhadriraju, K. & Chen, C.S. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6, 483–495 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Rape, A.D., Guo, W.H. & Wang, Y.L. The regulation of traction force in relation to cell shape and focal adhesions. Biomaterials 32, 2043–2051 (2011).

    Article  CAS  PubMed  Google Scholar 

  95. Thavandiran, N. et al. Design and formulation of functional pluripotent stem cell-derived cardiac microtissues. Proc. Natl. Acad. Sci. USA 110, E4698–E4707 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Yang, M.T., Reich, D.H. & Chen, C.S. Measurement and analysis of traction force dynamics in response to vasoactive agonists. Integr. Biol. (Camb.) 3, 663 (2011).

    Article  CAS  Google Scholar 

  97. Butler, J.P., Tolic-Norrelykke, I.M., Fabry, B. & Fredberg, J.J. Traction fields, moments, and strain energy that cells exert on their surroundings. Am. J. Physiol. Cell Physiol. 282, C595–C605 (2002).

    Article  CAS  PubMed  Google Scholar 

  98. Wang, N. et al. Cell prestress. I. Stiffness and prestress are closely associated in adherent contractile cells. Am. J. Physiol. Cell Physiol. 282, C606–C616 (2002).

    Article  CAS  PubMed  Google Scholar 

  99. Pelham, R.J. & Wang, Y.L. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl. Acad. Sci. USA 94, 13661–13665 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Meyers, M.A., Chen, P.-Y., Lin, A.Y.-M. & Seki, Y. Biological materials: structure and mechanical properties. Prog. Mater. Sci. 53, 1–206 (2008).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. Chopra and M. Kutys for helpful discussions. This work was supported in part by the US National Institutes of Health (NIH) (grants EB00262 and GM74048 to C.S.C.), the National Science Foundation (grant CMMI-1462710 to C.S.C.), and the RESBIO Technology Resource for Polymeric Biomaterials (grant P41-EB001046 to C.S.C.). W.J.P. acknowledges financial support from the NIH through the Organ Design and Engineering Training program (T32 EB16652).

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Polacheck, W., Chen, C. Measuring cell-generated forces: a guide to the available tools. Nat Methods 13, 415–423 (2016). https://doi.org/10.1038/nmeth.3834

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