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Microfabricated Stretching Devices for Studying the Effects of Tensile Stress on Cells and Tissues

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Abstract

Tensile stress is one of the most common mechanical stresses on the connective tissues of human organs. Cell stretching devices have been developed to study the effects of tensile stress on cells and tissues. In this study, we review how these devices function mechanically and apply them to biological research. To this end, we technically evaluate the four types of actuation processes used in cell stretching devices, including electric motor-driven and electromagnetic actuation, along with their pros and cons. For example, these cell stretching devices have shortcomings including large size, a complicated system, and generation of heat and shock, which hinder the real-time imaging of cells during stretching in high-resolution microscopes. We also describe the effects of tensile stress on cellular and tissue homeostasis. With this review, we seek to explore future directions for development of cell tensioning devices to understand mechanobiological responses to mechanical stress in vivo.

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References

  1. Wang, J.H.C., Thampatty, B.P.: An introductory review of cell mechanobiology. Biomech. Model. Mechanobiol 5, 1–16 (2006)

    Article  CAS  Google Scholar 

  2. Ingber, D.E.: Cellular mechanotransduction: putting all the pieces together again. FASEB J. 20, 811–827 (2006)

    Article  CAS  Google Scholar 

  3. Butcher, D.T., Alliston, T., Weaver, V.M.: A tense situation: forcing tumour progression. Nat. Rev. Cancer 9, 108–122 (2009)

    Article  CAS  Google Scholar 

  4. Sanderson, I.R.: The physicochemical environment of the neonatal intestine. Am. J. Clin. Nutr. 69, 1028s–1034s (1999)

    Article  CAS  Google Scholar 

  5. Wang, L., et al.: Biomechanical studies on biomaterial degradation and co-cultured cells: mechanisms, potential applications, challenges and prospects. J. Mater. Chem. B 7, 7439–7459 (2019)

    Article  CAS  Google Scholar 

  6. Huh, D., et al.: Reconstituting organ-level lung functions on a chip. Science 328, 1662–1668 (2010)

    Article  CAS  Google Scholar 

  7. Hoffman, B.D., Crocker, J.C.: Cell mechanics: dissecting the physical responses of cells to force. Annu. Rev. Biomed. Eng. 11, 259–288 (2009)

    Article  CAS  Google Scholar 

  8. Happe, C.L., Engler, A.J.: Mechanical forces reshape differentiation cues that guide cardiomyogenesis. Circ. Res. 118, 296–310 (2016)

    Article  CAS  Google Scholar 

  9. Aragona, M., et al.: A mechanical checkpoint controls multicellular growth through YAP1/TAZ regulation by actin-processing factors. Cell 154, 1047–1059 (2013)

    Article  CAS  Google Scholar 

  10. Labernadie, A., et al.: A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion. Nat. Cell Biol. 19, 224–237 (2017)

    Article  CAS  Google Scholar 

  11. Cai, X., Wang, K.C., Meng, Z.: Mechanoregulation of YAP and TAZ in cellular homeostasis and disease progression. Front. Cell Dev. Biol. 9, 673599 (2021)

    Article  Google Scholar 

  12. Silver, F.H., Siperko, L.M.: Mechanosensing and mechanochemical transduction: how is mechanical energy sensed and converted into chemical energy in an extracellular matrix? Crit. Rev. Biomed. Eng. 31, 255–331 (2003)

    Article  Google Scholar 

  13. DuFort, C.C., Paszek, M.J., Weaver, V.M.: Balancing forces: architectural control of mechanotransduction. Nat. Rev. Mol. Cell. Biol. 12, 308–319 (2011)

    Article  CAS  Google Scholar 

  14. Kamble, H., et al.: Cell stretching devices as research tools: engineering and biological considerations. Lab Chip 16, 3193–3203 (2016)

    Article  CAS  Google Scholar 

  15. Cui, Y., et al.: Cyclic stretching of soft substrates induces spreading and growth. Nat. Commun. 6, 1–8 (2015)

    Article  CAS  Google Scholar 

  16. Chiu, C.H., et al.: Osteogenesis and chondrogenesis of primary rabbit periosteal cells under non-uniform 2-axial tensile strain. BioChip J. 14, 438–446 (2020)

    Article  CAS  Google Scholar 

  17. Trepat, X., et al.: Universal physical responses to stretch in the living cell. Nature 447, 592–595 (2007)

    Article  CAS  Google Scholar 

  18. Kim, E.H., et al.: Effect of cyclic stretching on cell shape and division. BioChip J. 9, 306–312 (2015)

    Article  CAS  Google Scholar 

  19. Samak, G., et al.: Cyclic stretch disrupts apical junctional complexes in Caco-2 cell monolayers by a JNK-2-, c-Src-, and MLCK-dependent mechanism. Am. J. Physiol. Gastrointest. Liver Physiol. 306, 947–958 (2014)

    Article  Google Scholar 

  20. Lee, C.-F., et al.: Cyclic stretch-induced stress fiber dynamics–dependence on strain rate, Rho-kinase and MLCK. Biochem. Biophys. Res. Commun. 401, 344–349 (2010)

    Article  CAS  Google Scholar 

  21. Gudipaty, S.A., et al.: Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature 543, 118–121 (2017)

    Article  CAS  Google Scholar 

  22. Wyatt, T.P., et al.: Emergence of homeostatic epithelial packing and stress dissipation through divisions oriented along the long cell axis. Proc. Nat’l. Acad. Sci. U. S. A. 112, 5726–5731 (2015)

    Article  CAS  Google Scholar 

  23. Chang, Y.J., et al.: Micropatterned stretching system for the investigation of mechanical tension on neural stem cells behavior. Nanomedicine 9, 345–355 (2013)

    Article  CAS  Google Scholar 

  24. Ahn, J., et al.: A microfluidic stretch system upregulates resistance exercise-related pathway. BioChip J. (2022). https://doi.org/10.1007/s13206-022-00051-6

    Article  Google Scholar 

  25. Kaunas, R., et al.: Cooperative effects of Rho and mechanical stretch on stress fiber organization. Proc. Nat’l. Acad. Sci. U. S. A. 102, 15895–15900 (2005)

    Article  CAS  Google Scholar 

  26. Huang, L., et al.: A stretching device for high-resolution live-cell imaging. Ann. Biomed. Eng. 38, 1728–1740 (2010)

    Article  Google Scholar 

  27. Harshad, K., et al.: An electromagnetic cell-stretching device for mechanotransduction studies of olfactory ensheathing cells. Biomed. Microdevices 18, 45 (2016)

    Article  Google Scholar 

  28. Lim, H.Y., et al.: Development of wrinkled skin-on-a-chip (WSOC) by cyclic uniaxial stretching. J. Ind. Eng. Chem. 68, 238–245 (2018)

    Article  CAS  Google Scholar 

  29. Iwadate, Y., et al.: Cyclic stretch of the substratum using a shape-memory alloy induces directional migration in Dictyostelium cells. Biotechniques 47, 757–767 (2009)

    Article  CAS  Google Scholar 

  30. Wang, Q., et al.: A microscale mechanical stimulator for generating identical in-plane surface strains toward live cells on multiple loading sites. Sens. Actuators B Chem. 194, 484–491 (2014)

    Article  CAS  Google Scholar 

  31. Gopalan, S.M., et al.: Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers. Biotechnol. Bioeng. 81, 578–587 (2003)

    Article  CAS  Google Scholar 

  32. Zhao, X.-H., et al.: Force activates smooth muscle α-actin promoter activity through the Rho signaling pathway. J. Cell Sci. 120, 1801–1809 (2007)

    Article  CAS  Google Scholar 

  33. McGee, K.M., et al.: Nuclear transport of the serum response factor coactivator MRTF-A is downregulated at tensional homeostasis. EMBO rep. 12, 963–970 (2011)

    Article  CAS  Google Scholar 

  34. Dong, J., et al.: Elucidation of a universal size-control mechanism in Drosophila and mammals. Cell 130, 1120–1133 (2007)

    Article  CAS  Google Scholar 

  35. Eisenhoffer, G.T., et al.: Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature 484, 546–549 (2012)

    Article  CAS  Google Scholar 

  36. Coste, B., et al.: Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010)

    Article  CAS  Google Scholar 

  37. Singhvi, R., et al.: Engineering cell shape and function. Science 264, 696–698 (1994)

    Article  CAS  Google Scholar 

  38. Folkman, J., et al.: Role of cell shape in growth control. Nature 273, 345–349 (1978)

    Article  CAS  Google Scholar 

  39. Matter, K., et al.: Mammalian tight junctions in the regulation of epithelial differentiation and proliferation. Curr. Opin. Cell Biol. 17, 453–458 (2005)

    Article  CAS  Google Scholar 

  40. Madara, J.L.: Regulation of the movement of solutes across tight junctions. Annu. Rev. Physiol. 60, 143–159 (1998)

    Article  CAS  Google Scholar 

  41. DeMeo, M.T., et al.: Intestinal permeation and gastrointestinal disease. J. Clin. Gastroenterol. 34, 385–396 (2002)

    Article  Google Scholar 

  42. Bogoyevitch, M.A., et al.: Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases. Microbiol. Mol. 70, 1061–1095 (2006)

    Article  CAS  Google Scholar 

  43. Bogoyevitch, M.A., et al.: c-Jun N-terminal kinase (JNK) signaling: recent advances and challenges. Biochim. Biophys. Acta Proteins Proteom. 1804, 463–475 (2010)

    Article  CAS  Google Scholar 

  44. Chaturvedi, L.S., et al.: Repetitive deformation activates focal adhesion kinase and ERK mitogenic signals in human Caco-2 intestinal epithelial cells through Src and Rac1. J. Biol. Chem. 282, 14–28 (2007)

    Article  CAS  Google Scholar 

  45. Li, W., et al.: Integrin and FAK-mediated MAPK activation is required for cyclic strain mitogenic effects in Caco-2 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 280, G75–G87 (2001)

    Article  CAS  Google Scholar 

  46. Thiery, J.P.: Epithelial–mesenchymal transitions in tumour progression. Nat. Rev. Cancer 2, 442–454 (2002)

    Article  CAS  Google Scholar 

  47. Greenburg, G., et al.: Epithelia suspended in collagen gels can lose characteristics of migrating mesenchymal cells. J. Cell Biol. 95, 333–339 (1982)

    Article  CAS  Google Scholar 

  48. Heise, R.L., et al.: Mechanical stretch induces epithelial-mesenchymal transition in alveolarepithelia via hyaluronan activation of innate immunity. J. Biol. Chem. 286, 17435–17444 (2011)

    Article  CAS  Google Scholar 

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Acknowledgements

This research was equally supported by the Fostering Global Talents for Innovative Growth Program (P0008746) supervised by the Korean Institute for Advancement of Technology (KIAT) and by the Technology Innovation Program (Industrial Strategic Technology Development Program-Development of disease models based on 3D microenvironmental platforms mimicking multiple organs and evaluation of drug efficacy) (20008413) funded by the MOTIE (Ministry of Trade, Industry, and Energy) in Korea.

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  1. Jaewon Kim and Sein Kim contributed equally to the work.

Authors and Affiliations

  1. School of Mechanical Engineering, Sungkyunkwan University, Suwon, 16419, Korea

    Jaewon Kim & Sungsu Park

  2. Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Korea

    Sein Kim & Sungsu Park

  3. Department of Biophysics, Sungkyunkwan University, Suwon, 16419, Korea

    Shahab Uddin & Sungsu Park

  4. ScopeM (Scientific Center of Optical and Electron Microscopy), Institute of Biochemistry, ETH Zurich, HPM C52.2, Otto-Stern-Weg 3, CH-8093, Zurich, Switzerland

    Sung Sik Lee

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  1. Jaewon Kim
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Kim, J., Kim, S., Uddin, S. et al. Microfabricated Stretching Devices for Studying the Effects of Tensile Stress on Cells and Tissues. BioChip J 16, 366–375 (2022). https://doi.org/10.1007/s13206-022-00073-0

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