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Guided cell migration on a graded micropillar substrate

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Abstract

Cell migration is facilitated by the interaction of living cells and their local microenvironment. The local topography is one of the key factors regulating cell migration. Interaction between the surface topography and the cell behaviors is critical to understanding tissue development and regeneration. In this study, a dynamic mask photolithography technique has been utilized to fabricate a surface with graded micropillars. It has been demonstrated that the cells have been successfully guided to migrate from the sparse zone to the dense zone. The cell polarization angle has been characterized in both sparse zone and the dense zone. Compared to the dense zone, the cells in the sparse zone are more aligned along the direction of the micropillar spacing gradient, which enables the guided cell migration. Moreover, the effects of the micropillar spacing gradient, micropillar diameter, and micropillar height have been investigated in terms of the cell migration speed and cell spreading area. Finally, two issues significantly affecting the cell migration have been discussed: trapped cells between the micropillars and cell clusters.

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References

  1. Lara Rodriguez L, Schneider IC (2013) Directed cell migration in multi-cue environments. Integr Biol 5(11):1306–1323

    Google Scholar 

  2. Painter KJ (2009) Continuous models for cell migration in tissues and applications to cell sorting via differential chemotaxis. Bull Math Biol 71(5):1117

    MathSciNet  MATH  Google Scholar 

  3. Nie F-Q, Yamada M, Kobayashi J, Yamato M, Kikuchi A, Okano T (2007) On-chip cell migration assay using microfluidic channels. Biomaterials 28(27):4017–4022

    Google Scholar 

  4. Rennekampff H-O, Hansbrough JF, Kiessig V, Doré C, Sticherling M, Schröder J-M (2000) Bioactive interleukin-8 is expressed in wounds and enhances wound healing. J Surg Res 93(1):41–54

    Google Scholar 

  5. Berthier E, Surfus J, Verbsky J, Huttenlocher A, Beebe D (2010) An arrayed high-content chemotaxis assay for patient diagnosis. Integr Biol 2(11–12):630–638

    Google Scholar 

  6. Feng JF, Liu J, Zhang XZ, Zhang L, Jiang JY, Nolta J, Zhao M (2012) Guided migration of neural stem cells derived from human embryonic stem cells by an electric field. Stem Cells 30(2):349–355

    Google Scholar 

  7. Jacquemet G, Hamidi H, Ivaska J (2015) Filopodia in cell adhesion, 3D migration and cancer cell invasion. Curr Opin Cell Biol 36:23–31

    Google Scholar 

  8. Albuschies J, Vogel V (2013) The role of filopodia in the recognition of nanotopographies. Sci Rep 3:1658

    Google Scholar 

  9. Prager-Khoutorsky M, Goncharov I, Rabinkov A, Mirelman D, Geiger B, Bershadsky AD (2007) Allicin inhibits cell polarization, migration and division via its direct effect on microtubules. Cell Motil Cytoskelet 64(5):321–337

    Google Scholar 

  10. Devreotes P, Janetopoulos C (2003) Eukaryotic chemotaxis: distinctions between directional sensing and polarization. J Biol Chem 278(23):20445–20448

    Google Scholar 

  11. McCarthy JB, Furcht LT (1984) Laminin and fibronectin promote the haptotactic migration of B16 mouse melanoma cells in vitro. J Cell Biol 98(4):1474–1480

    Google Scholar 

  12. Lo C-M, Wang H-B, Dembo M, Wang Y-L (2000) Cell movement is guided by the rigidity of the substrate. Biophys J 79(1):144–152

    Google Scholar 

  13. Mycielska ME, Djamgoz MB (2004) Cellular mechanisms of direct-current electric field effects: galvanotaxis and metastatic disease. J Cell Sci 117(9):1631–1639

    Google Scholar 

  14. Park J, Kim D-H, Levchenko A (2018) Topotaxis: a new mechanism of directed cell migration in topographic ECM gradients. Biophys J 114(6):1257–1263

    Google Scholar 

  15. Kim D-H, Han K, Gupta K, Kwon KW, Suh K-Y, Levchenko A (2009) Mechanosensitivity of fibroblast cell shape and movement to anisotropic substratum topography gradients. Biomaterials 30(29):5433–5444

    Google Scholar 

  16. Park J, Kim D-H, Kim H-N, Wang CJ, Kwak MK, Hur E, Suh K-Y, An SS, Levchenko A (2016) Directed migration of cancer cells guided by the graded texture of the underlying matrix. Nat Mater 15(7):792

    Google Scholar 

  17. Hui J, Pang SW (2019) Cell migration on microposts with surface coating and confinement. Biosci Rep 39(2):BSR20181596

    Google Scholar 

  18. Wei J, Shi J, Wang B, Tang Y, Tu X, Roy E, Ladoux B, Chen Y (2016) Fabrication of adjacent micropillar arrays with different heights for cell studies. Microelectron Eng 158:22–25

    Google Scholar 

  19. Alapan Y, Younesi M, Akkus O, Gurkan UA (2016) Anisotropically stiff 3D micropillar niche induces extraordinary cell alignment and elongation. Adv Healthc Mater 5(15):1884–1892

    Google Scholar 

  20. Kim D-H, Provenzano PP, Smith CL, Levchenko A (2012) Matrix nanotopography as a regulator of cell function. J Cell Biol 197(3):351–360

    Google Scholar 

  21. Beussman KM, Rodriguez ML, Leonard A, Taparia N, Thompson CR, Sniadecki NJ (2016) Micropost arrays for measuring stem cell-derived cardiomyocyte contractility. Methods 94:43–50

    Google Scholar 

  22. Bayley G, Mallon P (2008) Surface studies of corona treated polydimethylsiloxane-block-polystyrene hybrid copolymer films. Polym Eng Sci 48(10):1923–1930

    Google Scholar 

  23. **a W, Liu W, Cui L, Liu Y, Zhong W, Liu D, Wu J, Chua K, Cao Y (2004) Tissue engineering of cartilage with the use of chitosan-gelatin complex scaffolds. J Biomed Mater Res B Appl Biomater 71(2):373–380

    Google Scholar 

  24. Bodas D, Khan-Malek C (2007) Hydrophilization and hydrophobic recovery of PDMS by oxygen plasma and chemical treatment—an SEM investigation. Sens Actuators B Chem 123(1):368–373

    Google Scholar 

  25. Krishnamoorthy S, Noorani B, Xu C (2019) Effects of encapsulated cells on the physical–mechanical properties and microstructure of gelatin methacrylate hydrogels. Int J Mol Sci 20(20):5061

    Google Scholar 

  26. Wadnap S, Krishnamoorthy S, Zhang Z, Xu C (2019) Biofabrication of 3D cell-encapsulated tubular constructs using dynamic optical projection stereolithography. J Mater Sci Mater Med 30(3):36

    Google Scholar 

  27. Merceron TK, Burt M, Seol Y-J, Kang H-W, Lee SJ, Yoo JJ, Atala A (2015) A 3D bioprinted complex structure for engineering the muscle–tendon unit. Biofabrication 7(3):035003

    Google Scholar 

  28. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302(5651):1704–1709

    Google Scholar 

  29. Chen Z, Li Y, Liu W, Zhang D, Zhao Y, Yuan B, Jiang X (2009) Patterning mammalian cells for modeling three types of naturally occurring cell–cell interactions. Angew Chem Int Ed 48(44):8303–8305

    Google Scholar 

  30. Xu H, Casillas J, Xu C (2019) Effects of printing conditions on cell distribution within microspheres during inkjet-based bioprinting. AIP Adv 9(9):095055

    Google Scholar 

  31. Collins T (2007) ImageJ for Microscopy. BioTechniques 43:S25–S30

    MathSciNet  Google Scholar 

  32. Saez A, Buguin A, Silberzan P, Ladoux B (2005) Is the mechanical activity of epithelial cells controlled by deformations or forces? Biophys J 89(6):L52–L54

    Google Scholar 

  33. Ghibaudo M, Saez A, Trichet L, Xayaphoummine A, Browaeys J, Silberzan P, Buguin A, Ladoux B (2008) Traction forces and rigidity sensing regulate cell functions. Soft Matter 4(9):1836–1843

    Google Scholar 

  34. Wu J, Mao Z, Tan H, Han L, Ren T, Gao C (2012) Gradient biomaterials and their influences on cell migration. Interface Focus 2(3):337–355

    Google Scholar 

  35. Doyle AD, Wang FW, Matsumoto K, Yamada KM (2009) One-dimensional topography underlies three-dimensional fibrillar cell migration. J Cell Biol 184(4):481–490

    Google Scholar 

  36. Huang Y-J, Samorajski J, Kreimer R, Searson PC (2013) The influence of electric field and confinement on cell motility. PLoS ONE 8(3):e59447

    Google Scholar 

  37. Ponti A, Machacek M, Gupton S, Waterman-Storer C, Danuser G (2004) Two distinct actin networks drive the protrusion of migrating cells. Science 305(5691):1782–1786

    Google Scholar 

  38. Tremel A, Cai A, Tirtaatmadja N, Hughes BD, Stevens GW, Landman KA, O’Connor AJ (2009) Cell migration and proliferation during monolayer formation and wound healing. Chem Eng Sci 64(2):247–253

    Google Scholar 

  39. Crouch AS, Miller D, Luebke KJ, Hu W (2009) Correlation of anisotropic cell behaviors with topographic aspect ratio. Biomaterials 30(8):1560–1567

    Google Scholar 

  40. Vernon RB, Gooden MD, Lara SL, Wight TN (2005) Microgrooved fibrillar collagen membranes as scaffolds for cell support and alignment. Biomaterials 26(16):3131–3140

    Google Scholar 

  41. Zhu P, Tseng N-H, **e T, Li N, Fitts-Sprague I, Peyton SR, Sun Y (2019) Biomechanical microenvironment regulates fusogenicity of breast cancer cells. ACS Biomater Sci Eng 5:3817–3827

    Google Scholar 

  42. Yang MT, Fu J, Wang Y-K, Desai RA, Chen CS (2011) Assaying stem cell mechanobiology on microfabricated elastomeric substrates with geometrically modulated rigidity. Nat Protoc 6(2):187–213

    Google Scholar 

  43. Zhang Y, Xu G, Lee RM, Zhu Z, Wu J, Liao S, Zhang G, Sun Y, Mogilner A, Losert W (2017) Collective cell migration has distinct directionality and speed dynamics. Cell Mol Life Sci 74(20):3841–3850

    Google Scholar 

  44. Rørth P (2009) Collective cell migration. Ann Rev Cell Dev 25:407–429

    Google Scholar 

  45. Trepat X, Chen Z, Jacobson K (2012) Cell migration. Compr Physiol 2(4):2369–2392

    Google Scholar 

  46. Trepat X, Wasserman MR, Angelini TE, Millet E, Weitz DA, Butler JP, Fredberg JJ (2009) Physical forces during collective cell migration. Nat Phys 5(6):426–430

    Google Scholar 

  47. Painter K (2009) Modelling cell migration strategies in the extracellular matrix. J Math Biol 58(4–5):511

    MathSciNet  MATH  Google Scholar 

  48. Raeber G, Lutolf M, Hubbell J (2007) Mechanisms of 3-D migration and matrix remodeling of fibroblasts within artificial ECMs. Acta Biomater 3(5):615–629

    Google Scholar 

  49. Koh B, Jeon H, Kim D, Kang D, Kim KR (2019) Effect of fibroblast co-culture on the proliferation, viability and drug response of colon cancer cells. Oncol Lett 17(2):2409–2417

    Google Scholar 

  50. Endaya B, Guan SP, Newman JP, Huynh H, Sia KC, Chong ST, Kok CY, Chung AY, Liu BB, Hui KM (2017) Human mesenchymal stem cells preferentially migrate toward highly oncogenic human hepatocellular carcinoma cells with activated EpCAM signaling. Oncotarget 8(33):54629

    Google Scholar 

  51. Zhao X, Jain S, Larman HB, Gonzalez S, Irvine DJ (2005) Directed cell migration via chemoattractants released from degradable microspheres. Biomaterials 26(24):5048–5063

    Google Scholar 

Download references

Acknowledgements

This work was partially supported by Texas Tech University start-up fund and National Natural Science Foundation of China (51709120).

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Authors and Affiliations

  1. Department of Industrial, Manufacturing, and Systems Engineering, Texas Tech University, Lubbock, TX, 79409, USA

    Srikumar Krishnamoorthy & Changxue Xu

  2. School of Naval Architecture and Ocean Engineering, Huazhong University of Science and Technology, Wuhan, 430074, China

    Zhengyi Zhang

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  1. Srikumar Krishnamoorthy
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  2. Zhengyi Zhang
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  3. Changxue Xu
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Correspondence to Changxue Xu.

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Krishnamoorthy, S., Zhang, Z. & Xu, C. Guided cell migration on a graded micropillar substrate. Bio-des. Manuf. 3, 60–70 (2020). https://doi.org/10.1007/s42242-020-00059-7

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