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Mechanical force drives the polarization and orientation of cells

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Abstract

Collective cell groups are organized to form specific patterns that play an important role in various physiological and pathological processes, such as tissue morphogenesis, wound healing, and cancer invasion. Compared to the behavior of single cells, which has been studied intensively from many aspects (cell migration, adhesion, polarization, proliferation, etc.) and at various scales (molecular, subcellular, and cellular), the behavior of multiple cells is less well understood, particularly from a quantitative perspective. In this paper, we present our recent studies of collective polarization and orientation of multiple cells through both experimental measurement and theoretical modeling, including cell behavior on/in 2D and 3D substrate/tissue. We find that collective cell behavior, including polarization, alignment, and migration, is closely related to local stress states in cell layers or tissue, which demonstrates the crucial role of mechanical forces in living organisms. Specifically, cells demonstrate preferential polarization and alignment along the maximum principal stress in the cell layer, and the cell aspect ratio increases with in-plane maximum shear stress, suggesting that the maximum shear stress is the underlying driving force of cell polarization and orientation. This theory of stress-driven cell behavior of polarization and orientation provides a new perspective for understanding cell behavior in living organisms and a guideline for tissue engineering in biomedical applications.

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References

  1. Friedl, P., Gilmour, D.: Collective cell migration in morphogenesis, regeneration and cancer. Nat. Rev. Mol. Cell Biol. 10, 445–457 (2009)

    Article  Google Scholar 

  2. Lecaudey, V., Gilmour, D.: Organizing moving groups during morphogenesis. Curr. Opin. Cell Biol. 18, 102–107 (2006)

    Article  Google Scholar 

  3. Rørth, P.: Collective guidance of collective cell migration. Trends Cell Biol. 17, 575–579 (2007)

    Article  Google Scholar 

  4. Khalil, A.A., Ilina, O., Gritsenko, P.G., et al.: Collective invasion in ductal and lobular breast cancer associates with distant metastasis. Clin. Exp. Metastasis 34, 421–429 (2017)

    Article  Google Scholar 

  5. Keller, R.: Shaping the vertebrate body plan by polarized embryonic cell movements. Science 298, 1950–1954 (2002)

    Article  Google Scholar 

  6. Singer, A.J., Clark, R.A.F.: Catenous wound healing. N. Engl. J. Med. 341, 738–746 (1999)

    Article  Google Scholar 

  7. Affolter, M., Bellusci, S., Itoh, N., et al.: Tube or not tube: remodeling epithelial tissues by branching morphogenesis. Dev. Cell 4, 11–18 (2003)

    Article  Google Scholar 

  8. Friedl, P., Locker, J., Sahai, E., et al.: Classifying collective cancer cell invasion. Nat. Cell Biol. 14, 777–783 (2012)

    Article  Google Scholar 

  9. Ruiz, S.A., Chen, C.S.: Emergence of Patterned stem cell differentiation within multicellular structures. Stem Cells 26, 2921–2927 (2008)

    Article  Google Scholar 

  10. Wan, L.Q., Ronaldson, K., Park, M., et al.: Micropatterned mammalian cells exhibit phenotype-specific left–right asymmetry. Proc. Natl. Acad. Sci. USA 108, 12295–12300 (2011)

    Article  Google Scholar 

  11. He, S., Liu, C., Li, X., et al.: Dissecting collective cell behavior in polarization and alignment on micropatterned substrates. Biophys. J. 109, 489–500 (2015)

    Article  Google Scholar 

  12. Tambe, D.T., Hardin, C.C., Angelini, T.E., et al.: Collective cell guidance by cooperative intercellular forces. Nat. Mater. 10, 469–475 (2011)

    Article  Google Scholar 

  13. Liu, C., He, S., Li, X., et al.: Mechanics of cell mechanosensing on patterned substrate. J. Appl. Mech. 83, 051014 (2016)

    Article  Google Scholar 

  14. Vedula, S.R.K., Leong, M.C., Lai, T.L., et al.: Emerging modes of collective cell migration induced by geometrical constraints. Proc. Natl. Acad. Sci. USA 109, 12974–12979 (2012)

    Article  Google Scholar 

  15. Doxzen, K., Vedula, S.R.K., Leong, M.C., et al.: Guidance of collective cell migration by substrate geometry. Integr. Biol. 5, 1026 (2013)

    Article  Google Scholar 

  16. Li, X., He, S., Xu, J., et al.: Cooperative contraction behaviors of a one-dimensional cell chain. Biophys. J. 115, 554–564 (2018)

    Article  Google Scholar 

  17. He, S., Su, Y., Ji, B., et al.: Some basic questions on mechanosensing in cell-substrate interaction. J. Mech. Phys. Solids 70, 116–135 (2014)

    Article  MathSciNet  MATH  Google Scholar 

  18. Badique, F., Stamov, D.R., Davidson, P.M., et al.: Directing nuclear deformation on micropillared surfaces by substrate geometry and cytoskeleton organization. Biomaterials 34, 2991–3001 (2013)

    Article  Google Scholar 

  19. Chalut, K.J., Kulangara, K., Giacomelli, M.G., et al.: Deformation of stem cell nuclei by nanotopographical cues. Soft Matter 6, 1675–1681 (2010)

    Article  Google Scholar 

  20. Chen, B., Ji, B.H., Gao, H.J.: Modeling active mechanosensing in cell–matrix interactions. Annu. Rev. Biophys. 44, 1–32 (2015)

    Article  Google Scholar 

  21. Sidani, M., Wyckoff, J., Xue, C.S., et al.: Probing the microenvironment of mammary tumors using multiphoton microscopy. J. Mammary Gland Biol. 11, 151–163 (2006)

    Article  Google Scholar 

  22. Wang, W.G., Goswami, S., Sahai, E., et al.: Tumor cells caught in the act of invading: their strategy for enhanced cell motility. Trends Cell Biol. 15, 138–145 (2005)

    Article  Google Scholar 

  23. Zhong, Y., Ji, B.: Impact of cell shape on cell migration behavior on elastic substrate. Biofabrication 5, 015011 (2013)

    Article  Google Scholar 

  24. Zhong, Y., Ji, B.: How do cells produce and regulate the driving force in the process of migration? Eur. Phys. J. Spec. Top. 223, 1373–1390 (2014)

    Article  Google Scholar 

  25. Lo, C.M., Wang, H.B., Dembo, M., et al.: Cell movement is guided by the rigidity of the substrate. Biophys. J. 79, 144–152 (2000)

    Article  Google Scholar 

  26. Trepat, X., Wasserman, M.R., Angelini, T.E., et al.: Physical forces during collective cell migration. Nat. Phys. 5, 426–430 (2009)

    Article  Google Scholar 

  27. Chong, B., Gong, Z., Lin, Y.: Modeling the adhesive contact between cells and a wavy extracellular matrix mediated by receptor–ligand interactions. J. Appl. Mech. 84, 011010 (2017)

    Article  Google Scholar 

  28. Yang, L., Gong, Z., Lin, Y., et al.: Disordered topography mediates filopodial extension and morphology of cells on stiff materials. Adv. Funct. Mater. 27, 1702689 (2017)

    Article  Google Scholar 

  29. Hwang, C.M., Park, Y., Park, J.Y., et al.: Controlled cellular orientation on PLGA microfibers with defined diameters. Biomed. Microdevice 11, 739–746 (2009)

    Article  Google Scholar 

  30. Svitkina, T.M., Rovensky, Y.A., Bershadsky, A.D., et al.: Transverse pattern of microfilament bundles induced in epitheliocytes by cylindrical substrata. J. Cell Sci. 108, 735–745 (1995)

    Google Scholar 

  31. Bidan, C.M., Kommareddy, K.P., Rumpler, M., et al.: How linear tension converts to curvature: geometric control of bone tissue growth. PLoS ONE 7, e36336 (2012)

    Article  Google Scholar 

  32. Rumpler, M., Woesz, A., Dunlop, J.W., et al.: The effect of geometry on three-dimensional tissue growth. J. R. Soc. Interface/R. Soc. 5, 1173–1180 (2008)

    Article  Google Scholar 

  33. Pilia, M., Guda, T., Shiels, S.M., et al.: Influence of substrate curvature on osteoblast orientation and extracellular matrix deposition. J. Biol. Eng. 7, 23 (2013)

    Article  Google Scholar 

  34. Serra-Picamal, X., Conte, V., Vincent, R., et al.: Mechanical waves during tissue expansion. Nat. Phys. 8, 628–634 (2012)

    Article  Google Scholar 

  35. Zhong, Y., Kong, D., Dai, L., et al.: Frequency-dependent focal adhesion instability and cell reorientation under cyclic substrate stretching. Cell. Mol. Bioeng. 4, 442–456 (2011)

    Article  Google Scholar 

  36. Deguchi, S., Ohashi, T., Sato, M.: Tensile properties of single stress fibers isolated from cultured vascular smooth muscle cells. J. Biomech. 39, 2603–2610 (2006)

    Article  Google Scholar 

  37. Lu, L., Feng, Y., Hucker, W.J., et al.: Actin stress fiber pre-extension in human aortic endothelial cells. Cell Motil. Cytoskelet. 65, 281–294 (2008)

    Article  Google Scholar 

  38. Nelson, C.M., Jean, R.P., Tan, J.L., et al.: Emergent patterns of growth controlled by multicellular form and mechanics. Proc. Natl. Acad. Sci. USA 102, 11594–11599 (2005)

    Article  Google Scholar 

  39. Luo, W., Jones, S.R., Yousaf, M.N.: Geometric control of stem cell differentiation rate on surfaces. Langmuir 24, 12129–12133 (2008)

    Article  Google Scholar 

  40. Thery, M.: Micropatterning as a tool to decipher cell morphogenesis and functions. J Cell Sci. 123, 4201–4213 (2010)

    Article  Google Scholar 

  41. Liu, C., Xu, J., He, S., et al.: Collective cell polarization and alignment on curved surfaces. J. Mech. Behav. Biomed. Mater. 88, 330–339 (2018)

    Article  Google Scholar 

  42. Lammerding, J., Schulze, P.C., Takahashi, T., et al.: Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Investig. 113, 370–378 (2004)

    Article  Google Scholar 

  43. Dahl, K.N., Kahn, S.M., Wilson, K.L., et al.: The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J. Cell Sci. 117, 4779–4786 (2004)

    Article  Google Scholar 

  44. Khatau, S.B., Kim, D.H., Hale, C.M., et al.: The perinuclear actin cap in health and disease. Nucleus 1, 337–342 (2010)

    Article  Google Scholar 

  45. Horne-Badovinac, S., Bilder, D.: Mass transit: epithelial morphogenesis in the Drosophila egg chamber. Dev. Dyn. 232, 559–574 (2005)

    Article  Google Scholar 

  46. Kolahi, K.S., White, P.F., Shreter, D.M., et al.: Quantitative analysis of epithelial morphogenesis in Drosophila oogenesis: new insights based on morphometric analysis and mechanical modeling. Dev. Biol. 331, 129–139 (2009)

    Article  Google Scholar 

  47. Li, X., Ji, B.: Polarization and arrangement of epithelial cells in the embryonic development of Drosophila. J. Med. Biomech. 33, 291–299 (2018)

    Google Scholar 

  48. Eskandari, M., Pfaller, M., Kuhl, E.: On the role of mechanics in chronic lung disease. Materials 6, 5639–5658 (2013)

    Article  Google Scholar 

  49. Latorre, E., Kale, S., Casares, L., et al.: Active superelasticity in three-dimensional epithelia of controlled shape. Nature 563, 203–208 (2018)

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grants 11772055, 11532009, 11521062, 11372042).

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Correspondence to Baohua Ji.

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He, S., Li, X. & Ji, B. Mechanical force drives the polarization and orientation of cells. Acta Mech. Sin. 35, 275–288 (2019). https://doi.org/10.1007/s10409-019-00864-z

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  • DOI: https://doi.org/10.1007/s10409-019-00864-z

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