Directing cell function and fate via micropatterning: Role of cell patterning size, shape, and interconnectivity

Abstract

Micropatterning-based geometric cell confinement provides novel templates for investigating cellular function and fate. Cell size, shape, and degree of connectivity among cells can be systematically manipulated using micropatterning, allowing for the studies of the effects of patterned cell geometries on cell behavior. Cells conformed to micropatterns develop unique intracellular architectures and signaling activities, regulating cell proliferation, migration, survival/apoptosis, commitment, and differentiation. Cell patterning size controls cell survival and apoptosis and stem cell fate via cytoskeletal tension signaling such as RhoA-ROCK. Cell patterning shape affects cell growth and migration via altered cellular polarity and Rac1 signaling. Modulation of cell-cell interconnectivity via micropatterning affects proliferation and differentiation via regulating the expression of cell-cell interaction molecules such as cadherin. Systematic assessment of cell function and fate using micropatterned cells will shed new insights for understanding the mechanisms in cell and molecular biology studies and for the control of cell behavior in biomedical applications.

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References

  1. [1]

    Wang N, Ingber DE. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. J Bioph. 1994; 66(6):2181–2189.

    Article  Google Scholar 

  2. [2]

    Corey JM, Feldman EL. Substrate patterning: An emerging technology for the study of neuronal behavior. Exp Neurol. 2003; 184Suppl 1:S89–S96.

    Article  Google Scholar 

  3. [3]

    Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Geometric control of cell life and death. Science. 1997; 276(5317):1425–1428.

    Article  Google Scholar 

  4. [4]

    Chen CS, Mrksich M, Huang S, Whitesides GM, Ingber DE. Micropatterned surfaces for control of cell shape, position, and function. Biotech Prog. 1998; 14(3):356–363.

    Article  Google Scholar 

  5. [5]

    Yang IH, Co CC, Ho CC. Alteration of human neuroblastoma cell morphology and neurite extension with micropatterns. Biomaterials. 2005; 26(33):6599–609.

    Article  Google Scholar 

  6. [6]

    Frimat JP, Sisnaiske J, Subbiah S, Menne H, Godoy P, Lampen P, Leist M, Franzke J, Hengstler JG, van Thriel C, West J. The network formation assay: A spatially standardized neurite outgrowth analytical display for neurotoxicity screening. Lab Chip. 2010; 10(6):701–709.

    Article  Google Scholar 

  7. [7]

    Jiang X, Ferrigno R, Mrksich M, Whitesides GM. Electrochemical desorption of self-assembled monolayers noninvasively releases patterned cells from geometrical confinements. J Am Chem Soc. 2003; 125(9):2366–2367.

    Article  Google Scholar 

  8. [8]

    Kushiro K, Chang S, Asthagiri AR. Reprogramming directional cell motility by tuning micropattern features and cellular signals. Advan Mater. 2010; 22(40):4516–4519.

    Article  Google Scholar 

  9. [9]

    Rosenthal A, Macdonald A, Voldman J. Cell patterning chip for controlling the stem cell microenvironment. Biomaterials. 2007; 28(21):3208–3216.

    Article  Google Scholar 

  10. [10]

    Thery M. Micropatterning as a tool to decipher cell morphogenesis and functions. J Cell Sci. 2010; 123(24):4201–13.

    Article  Google Scholar 

  11. [11]

    McBeath R, Pirone DM, Nelson CM, Bhadriraju K, Chen CS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004; 6(4):483–495.

    Article  Google Scholar 

  12. [12]

    Lim JY, Donahue HJ. Cell sensing and response to micro- and nanostructured surfaces produced by chemical and topographic patterning. Tissue Eng. 2007; 13(8):1879–1891.

    Article  Google Scholar 

  13. [13]

    Ostuni E, Whitesides GM, Ingber DE, Chen CS. Using selfassembled monolayers to pattern ECM proteins and cells on substrates. Method Mol Biol. 2009; 522:183–194.

    Article  Google Scholar 

  14. [14]

    Lussi JW, Michel R, Reviakine I, Falconnet D, Goessl A, Csucs G, Hubbell JA, Textor M. A novel generic platform for chemical patterning of surfaces. Prog Surf Sci. 2004; 76:55–69.

    Article  Google Scholar 

  15. [15]

    Falconnet D, Koenig A, Assi T, Textor M. A combined photolithographic and molecular-assembly approach to produce functional micropatterns for applications in the biosciences. Adv Funct Mater. 2004; 14:749–756.

    Article  Google Scholar 

  16. [16]

    Lahann J, Mitragotri S, Tran TN, Kaido H, Sundaram J, Choi IS, Hoffer S, Somorjai GA, Langer R. A reversibly switching surface. Science. 2003; 299(5605):371–374.

    Article  Google Scholar 

  17. [17]

    Kidambi S, Lee I, Chan C. Patterned co-culture of neurons and astrocytes on polyelectrolyte multilayer films for studying astrocyte mediated oxidative stress in neurons. Adv Funct Mater. 2008; 18:294–301.

    Article  Google Scholar 

  18. [18]

    Folch A, Jo BH, Hurtado O, Beebe DJ, Toner M. Microfabricated elastomeric stencils for micropatterning cell cultures. J Biomed Mater Res. 2000; 52(2):346–353.

    Article  Google Scholar 

  19. [19]

    Rettig JR, Folch A. Large-scale single-cell trapping and imaging using microwell arrays. Anal Chem. 2005; 77(17):5628–34.

    Article  Google Scholar 

  20. [20]

    Shi J, Ahmed D, Mao X, Lin SC, Lawit A, Huang TJ. Acoustic tweezers: patterning cells and microparticles using standing surface acoustic waves (SSAW). Lab Chip. 2009; 9(20):2890–2895.

    Article  Google Scholar 

  21. [21]

    Albrecht DR, Underhill GH, Wassermann TB, Sah RL, Bhatia SN. Probing the role of multicellular organization in threedimensional microenvironments. Nat Methods. 2006; 3(5):369–375.

    Article  Google Scholar 

  22. [22]

    Gray DS, Liu WF, Shen CJ, Bhadriraju K, Nelson CM, Chen CS. Engineering amount of cell-cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton. Exp Cell Res. 2008; 314(15):2846–2854.

    Article  Google Scholar 

  23. [23]

    Buyukhatipoglu K, Chang R, Sun W, Clyne AM. Bioprinted nanoparticles for tissue engineering applications. Tissue Eng Part C Meth. 2010; 16(4):631–642.

    Article  Google Scholar 

  24. [24]

    Buzanska L, Zychowicz M, Ruiz A, Ceriotti L, Coecke S, Rauscher H, Sobanski T, Whelan M, Domanska-Janik K, Colpo P, Rossi F. Neural stem cells from human cord blood on bioengineered surfaces-novel approach to multiparameter biotests. Toxicol. 2010; 270(1):35–42.

    Article  Google Scholar 

  25. [25]

    El-Amraoui A, Petit C. Cadherins as targets for genetic diseases. Cold Spring Harb Perspect Biol. 2010; 2(1):a003095.

    Article  Google Scholar 

  26. [26]

    Chen CS, Alonso JL, Ostuni E, Whitesides GM, Ingber DE. Cell shape provides global control of focal adhesion assembly. Biochem Biophys Res Commun. 2003; 307(2):355–361.

    Article  Google Scholar 

  27. [27]

    Watt FM, Jordan PW, O’Neill CH. Cell shape controls terminal differentiation of human epidermal keratinocytes. P Natl Acad Sci USA. 1988; 85(15):5576–5580.

    Article  Google Scholar 

  28. [28]

    Ingber D. Extracellular matrix and cell shape: Potential control points for inhibition of angiogenesis. J Cell Biochem. 1991; 47(3):236–41.

    Article  Google Scholar 

  29. [29]

    Lim JY, Taylor AF, Li Z, Vogler EA, Donahue HJ. Integrin expression and osteopontin regulation in human fetal osteoblastic cells mediated by substratum surface characteristics. Tissue Eng. 2005; 11(1–2):19–29.

    Article  Google Scholar 

  30. [30]

    Lim JY, Shaughnessy MC, Zhou Z, Noh H, Vogler EA, Donahue HJ. Surface energy effects on osteoblast spatial growth and mineralization. Biomaterials. 2008; 29(12):1776–1784.

    Article  Google Scholar 

  31. [31]

    Song W, Lu H, Kawazoe N, Chen G. Adipogenic differentiation of individual mesenchymal stem cell on different geometric micropatterns. Langmuir. 2011; 27(10):6155–162.

    Article  Google Scholar 

  32. [32]

    Gao L, McBeath R, Chen CS. Stem cell shape regulates a chondrogenic versus myogenic fate through Rac1 and Ncadherin. Stem Cells. 2010; 28(3):564–572.

    Google Scholar 

  33. [33]

    Thomas CH, Collier JH, Sfeir CS, Healy KE. Engineering gene expression and protein synthesis by modulation of nuclear shape. P Natl Acad Sci USA. 2002; 99(4):1972–1977.

    Article  Google Scholar 

  34. [34]

    Jiang X, Bruzewicz DA, Wong AP, Piel M, Whitesides GM. Directing cell migration with asymmetric micropatterns. P Natl Acad Sci USA. 2005; 102(4):975–978.

    Article  Google Scholar 

  35. [35]

    Kumar G, Ho CC, Co CC. Guiding cell migration using one-way micropattern arrays. Adv Mater. 2007; 19:1084–90.

    Article  Google Scholar 

  36. [36]

    Nelson CM, Jean RP, Tan JL, Liu WF, Sniadecki NJ, Spector AA, Chen CS. Emergent patterns of growth controlled by multicellular form and mechanics. P Natl Acad Sci USA. 2005; 102(33):11594–11599.

    Article  Google Scholar 

  37. [37]

    Nishimura T, Takeichi M. Remodeling of the adherens junctions during morphogenesis. Curr Top Dev Biol. 2009; 89:33–54.

    Article  Google Scholar 

  38. [38]

    Stains JP, Civitelli R. Cell-to-cell interactions in bone. Biochem Bioph Res Co. 2005; 328(3):721–727.

    Article  Google Scholar 

  39. [39]

    Zhang Y, Paul EM, Sathyendra V, Davison A, Sharkey N, Bronson S, Srinivasan S, Gross TS, Donahue HJ. Enhanced osteoclastic resorption and responsiveness to mechanical load in gap junction deficient bone. PLoS One. 2011; 6(8):e23516.

    Article  Google Scholar 

  40. [40]

    Bloemen V, Schoenmaker T, de Vries TJ, Everts V. Direct cellcell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis. J Cell Physiol. 2010; 222(3):565–573.

    Google Scholar 

  41. [41]

    Charest JL, Jennings JM, King WP, Kowalczyk AP, Garcia AJ. Cadherin-mediated cell-cell contact regulates keratinocyte differentiation. J Invest Dermatol. 2009; 129(3):564–572.

    Article  Google Scholar 

  42. [42]

    Cukierman E, Pankov R, Stevens DR, Yamada KM. Taking cell-matrix adhesions to the third dimension. Science. 2001; 294(5547):1708–12.

    Article  Google Scholar 

  43. [43]

    Xu Y, Yao H, Wang L, Xing W, Cheng J. The construction of an individually addressable cell array for selective patterning and electroporation. Lab Chip. 2011; 11(14):2417–2423.

    Article  Google Scholar 

  44. [44]

    Fedorovich NE, Alblas J, Hennink WE, Oner FC, Dhert WJ. Organ printing: the future of bone regeneration? Trends Biotechnol. 2011; 29(12):601–606.

    Article  Google Scholar 

  45. [45]

    Gruene M, Pflaum M, Hess C, Diamantouros S, Schlie S, Deiwick A, Koch L, Wilhelmi M, Jockenhoevel S, Haverich A, Chichkov B. Laser printing of three-dimensional multicellular arrays for studies of cell-cell and cell-environment interactions. Tissue Eng Part C Method. 2011; 17(10):973–982.

    Article  Google Scholar 

  46. [46]

    Hanson Shepherd JN, Parker ST, Shepherd RF, Gillette MU, Lewis JA, Nuzzo RG. 3D Microperiodic Hydrogel Scaffolds for Robust Neuronal Cultures. Adv Funct Mater. 2011; 21(1):47–54.

    Article  Google Scholar 

  47. [47]

    Park JY, Takayama S, Lee SH. Regulating microenvironmental stimuli for stem cells and cancer cells using microsystems. Integr Biol (Camb). 2010; 2(5–6):229–240.

    Article  Google Scholar 

  48. [48]

    Kim S, Kim HJ, Jeon NL. Biological applications of microfluidic gradient devices. Integr Biol (Camb). 2010; 2(11–12):584–603.

    MathSciNet  Article  Google Scholar 

  49. [49]

    Moraes C, Sun Y, Simmons CA. (Micro)managing the mechanical microenvironment. Integr Biol (Camb). 2011; 3(10):959–971.

    Article  Google Scholar 

  50. [50]

    Tavana H, Jovic A, Mosadegh B, Lee QY, Liu X, Luker KE, Luker GD, Weiss SJ, Takayama S. Nanolitre liquid patterning in aqueous environments for spatially defined reagent delivery to mammalian cells. Nat Mater. 2009; 8(9):736–741.

    Article  Google Scholar 

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Correspondence to Jung Yul Lim.

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Poudel and Menter contributed equally.

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Poudel, I., Menter, D.E. & Lim, J.Y. Directing cell function and fate via micropatterning: Role of cell patterning size, shape, and interconnectivity. Biomed. Eng. Lett. 2, 38–45 (2012). https://doi.org/10.1007/s13534-012-0045-z

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Keywords

  • Micropatterning
  • Geometric confinement
  • Cell size
  • Shape
  • Interconnectivity