Cell Biochemistry and Biophysics

, Volume 45, Issue 2, pp 215–227

Living in three dimensions

3D nanostructured environments for cell culture and regenerative medicine
  • Melvin Schindler
  • Alam Nur-E-Kamal
  • Ijaz Ahmed
  • Jabeen Kamal
  • Hsing-Yin Liu
  • Nathan Amor
  • Abdul S. Ponery
  • David P. Crockett
  • Timothy H. Grafe
  • H. Young Chung
  • Thom Weik
  • Elizabeth Jones
  • Sally Meiners


Research focused on deciphering the biochemical mechanisms that regulate cell proliferation and function has largely depended on the use of tissue culture methods in which cells are grown on two-dimensional (2D) plastic or glass surfaces. However, the flat surface of the tissue culture plate represents a poor topological approximation of the more complex three-dimensional (3D) architecture of the extracellular matrix (ECM) and the basement membrane (BM), a structurally compact form of the ECM. Recent work has provided strong evidence that the highly porous nanotopography that results from the 3D associations of ECM and BM nanofibrils is essential for the reproduction of physiological patterns of cell adherence, cytoskeletal organization, migration, signal transduction, morphogenesis, and differentiation in cell culture. In vitro approximations of these nanostructured surfaces are therefore desirable for more physiologically mimetic model systems to study both normal and abnormal functions of cells, tissues, and organs. In addition, the development of 3D culture environments is imperative to achieve more accurate cell-based assays of drug sensitivity, high-throughput drug discovery assays, and in vivo and ex vivo growth of tissues for applications in regenerative medicine.

Index Entries

Extracellular matrix basement membrane 2D 3D nanofibrillar tissue culture regenerative medicine 


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  1. 1.
    Berthiaume, F., Moghe, P. V., Toner, M., and Yarmush, M. L. (1996) Effect of extracellular matrix topology on cell structure, function, and physiological responsiveness: hepatocytes cultured in a sandwich configuration. FASEB J. 10, 1471–1484.PubMedGoogle Scholar
  2. 2.
    Knedlitschek, G., Schneider, F., Gottwald, E., Schaller, T., Eschbach, E., and Weibezahn, K. F. (1999) A tissue-like culture system using microstructures: influence of extracellular matrix material on cell adhesion and aggregation. J. Biomech. Eng. 121, 35–39.PubMedGoogle Scholar
  3. 3.
    Ertel, S. I., Chilkoti, A., Horbett, T. A., and Ratner, B. D. (1991) Endothelial cell growth on oxygen-containing films deposited by radio-frequency plasmas; the role of surface carbonyl groups. Biomater. Sci. Polym. Ed. 3, 163–183.Google Scholar
  4. 4.
    Hojo, M., Inokuchi, S., Kidokoro, M., et al. (2003) Induction of vascular endothelial growth factor by fibrin as a dermal substrate for cultured skin substitute. Plast. Reconstr. Surg. 111, 1638–1645.PubMedCrossRefGoogle Scholar
  5. 5.
    Kim, B. S., Nikolovski, J., Bonadio, J., Smiley, E., and Mooney, D. J. (1999) Engineered smooth muscle tissues: regulating cell phenotype with the scaffold, Exper. Cell. Res. 251, 318–328.CrossRefGoogle Scholar
  6. 6.
    Sakiyama, S. E., Schense, J. C., and Hubbell, J. A. (1999) Incorporation of heparin-binding peptides into fibrin gels enhances neurite extension: an example of designer matrices in tissue engineering, FASEB J. 13, 2214–2224.PubMedGoogle Scholar
  7. 7.
    Lutolf, M. P., Lauer-Fields, J. L., Schmoekel, H. G., et al. (2003) Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: Engineering cell-invasion characteristics. Proc. Natl. Acad. Sci. USA 100, 5413–5418.PubMedCrossRefGoogle Scholar
  8. 8.
    Bottaro, D. P., Liebmann-Vinson, A., and Heidaran, M. A. (2002) Molecular signaling in bioengineered tissue microenvironments. Ann. N. Y. Acad. Sci. 961, 143–153.PubMedCrossRefGoogle Scholar
  9. 9.
    Alsberg, E., Anderson, K. W., Albeiruti, A., Rowley, J. A., and Mooney, D. J. (2002) Engineering growing tissues. Proc. Natl. Acad. Sci. USA 99, 12025–12030.PubMedCrossRefGoogle Scholar
  10. 10.
    Stegman, J. P. and Nerem, R. M. (2003) Altered response of vascular smooth muscle cells to exogenous biochemical stimulation in two- and three-dimensional culture. Exp. Cell. Res. 283, 146–155.CrossRefGoogle Scholar
  11. 11.
    Walpita, D. and Hay, E. (2002) Studying actin-dependent processes in tissue culture. Nat. Rev. Mol. Rev. Mol. Cell Biol. 3, 137–141.CrossRefGoogle Scholar
  12. 12.
    Mueller-Klieser, W. (1997) Three dimensional cell cultures: from molecular mechanisms to clinical applications. Am. J. Physiol. (Cell Physiol.) 42, C1109-C1123.Google Scholar
  13. 13.
    Grinnell, F., Ho, C.-H., Tamariz, E., Lee, D. J., and Skuta, G. (2003) Dendritic fibroblasts in three-dimensional collagen matrices. Mol. Biol. Cell. 14, 384–395.PubMedCrossRefGoogle Scholar
  14. 14.
    Abbott, A. (2003) Cell culture: biology's new dimension. Nature 424, 870–872.PubMedCrossRefGoogle Scholar
  15. 15.
    Kalluri, R. (2003) Basement membranes: structure, assembly and role in tumour angiogenesis. Nat. Rev. Cancer 3, 422–433.PubMedCrossRefGoogle Scholar
  16. 16.
    Ashkenas, J., Muschler, J., and Bissell, M. J. (1996) The extracellular matrix in epithelial biology: shared molecules and common themes in distant phyla. Dev. Biol. 180, 433–444.PubMedCrossRefGoogle Scholar
  17. 17.
    Hay, E. D. (2005) The mesenchymal cell, its role in the embryo, and the remarkable signaling mechanisms that create it. Dev. Dyn. 233, 706–720.PubMedCrossRefGoogle Scholar
  18. 18.
    Boudreau, N. J. (2003) Organized living: from cell surfaces to basement membranes. Sci. STKE 196, pe34.Google Scholar
  19. 19.
    Miner, J. H. and Yurchenco, P. D. (2004) Laminin functions in tissue morphogenesis. Annu. Rev. Cell Dev. Biol. 20, 255–284.PubMedCrossRefGoogle Scholar
  20. 20.
    Michelacci, Y. M. (2003) Collagens and proteoglycans of the corneal extracellular matrix. Braz. J. Med. Biol. Res. 36, 1037–1046.PubMedCrossRefGoogle Scholar
  21. 21.
    Abrams, G. A., Goodman, S. L., Nealy, P. F., Franco, M., and Murphy, C. J. (2000) Nanoscale topography of the basement membrane underlying the corneal epithelium of the Rhesus macaque. Cell Tissue Res. 299, 39–46.PubMedCrossRefGoogle Scholar
  22. 22.
    Petersen, O. W., Ronnow-Jessen, L., Howlett, A. R., and Bissell, M. J. (1992) Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc. Natl. Acad. Sci. USA 89, 9064–9068.PubMedCrossRefGoogle Scholar
  23. 23.
    Schmeichel, K. L. and Bissell, M. J. (2003) Modeling tissue-specific signaling and organ function in three dimensions. J. Cell. Sci. 116, 2377–2388.PubMedCrossRefGoogle Scholar
  24. 24.
    Weaver, V. M., Lelievre, S., Lakins, J. N. et al. (2002) β-4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2, 205–216.PubMedCrossRefGoogle Scholar
  25. 25.
    Kleinman, H. K., Philp, D., and Hoffman, M. P. (2003) Role of the extracellular matrix in morphogenesis. Curr. Op. Biotech. 14, 526–532.CrossRefGoogle Scholar
  26. 26.
    Cukierman, E., Pankov, R., Stevens, D. R., and Yamada, K. M. (2001) Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712.PubMedCrossRefGoogle Scholar
  27. 27.
    Katz, B. Z., Zamir, E., Bershadsky, A., Kam, Z., Yamada, K. M., and Geiger, B. (2000) Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol. Biol. Cell 11, 1047–1060.PubMedGoogle Scholar
  28. 28.
    Cukierman, E., Pankov, R., and Yamada, K. M. (2002) Cell interactions with three-dimensional matrices. Curr. Opin. Cell. Biol. 14, 633–639.PubMedCrossRefGoogle Scholar
  29. 29.
    Wang, H. B., Dembo, M., Hanks, S. K., and Wang, Y-L. (2001) Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl. Acad. Sci. USA 98, 11295–11300.PubMedCrossRefGoogle Scholar
  30. 30.
    Meiners, S. and Mercado, M. L. (2003) Functional peptide sequences derived from extracellular matrix glycoproteins and their receptors: strategies to improve neuronal regeneration. Mol. Neurobiol. 27, 177–196.PubMedCrossRefGoogle Scholar
  31. 31.
    Shin, H., Jo, S., and Mikos, A. G. (2003) Biomimetic materials for tissue engineering. Biomaterials 24, 4353–4364.PubMedCrossRefGoogle Scholar
  32. 32.
    Vlodavsky, I. (1999) Preparation of extracellular matrices produced by cultured corneal endothelial and PF-HR9 endodermal cells, in Current Protocols in Cell Biology, Vol. 1 (Bonifacino, J., Dasso, M., Harford, J., Lippincott-Schwartz, J., and Yamada, K. M., eds), John Wiley & Sons, New York, pp. 10.14.11–10.14.14.Google Scholar
  33. 33.
    Zamir, E. and Geiger, B. (2001) Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 14, 3583–3590.Google Scholar
  34. 34.
    Wozniak, M. A., Modzelewska, K., Kwong, L., and Keely, P. (2004) Focal adhesion regulation of cell behavior. Biochim. Biophys. Acta. 1692, 103–119.PubMedGoogle Scholar
  35. 35.
    Dhiman, H. K., Ray, A. R., and Panda, A. K. (2005) Three-dimensional chitosan scaffold-based MCF-7 cell culture for the determination of the cytotoxicity of tamoxifen. Biomaterials 26, 979–986.PubMedCrossRefGoogle Scholar
  36. 36.
    Pogany, G., Timar, F., Olah, J., et al. (2001) Role of the basement membrane in tumor cell dormancy and cytotoxic resistance. Oncology 60, 274–281.PubMedCrossRefGoogle Scholar
  37. 37.
    Shain, K. H. and Dalton, W. S. (2001) Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR. Mol. Cancer Ther. 1, 69–78.PubMedGoogle Scholar
  38. 38.
    Buttery, R. C., Rintoul, R. C., and Sethi, T. (2004) Small cell lung cancer: the importance of the extracellular matrix. Int. J. Biochem. Cell. Biol. 36, 1154–1160.PubMedCrossRefGoogle Scholar
  39. 39.
    Balis, F. M. (2002) Evolution of anticancer drug discovery and the role of cell-based screening. J. Natl. Cancer Inst. 94, 78–79.PubMedGoogle Scholar
  40. 40.
    Friedl, P. (2004) Prespecification and plasticity: shifting mechanisms of cell migration. Curr. Op. Cell. Biol. 16, 14–23.PubMedCrossRefGoogle Scholar
  41. 41.
    Lauffenburger, D. A. and Horwitz, A. F. (1996) Cell migration: a physically integrated molecular process. Cell 84, 359–369.PubMedCrossRefGoogle Scholar
  42. 42.
    Sahai, E. and Marshall, C. J. (2003) Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signaling and extracellular proteolysis. Nat. Cell Biol. 5, 711–719.PubMedCrossRefGoogle Scholar
  43. 43.
    Meshel, A. S., Wei, Q., Adelstein, R. S., and Sheetz, M. P. (2005) Basic mechanism of three-dimensional collagen fibre transport by fibroblasts. Nat. Cell. Biol. 7, 157–164.PubMedCrossRefGoogle Scholar
  44. 44.
    Condeelis, J. and Segall, J. E. (2003) Intravital imaging of cell movement in tumours. Nat. Rev. Cancer 3, 921–930.PubMedCrossRefGoogle Scholar
  45. 45.
    Knight, B., Laukaitis, C., Akhtar, N., Hotchin, N. A., Edlund, M., and Horwitz, A. R. (2000) Visualizing muscle cell migration in situ. Curr. Biol. 10, 576–585.PubMedCrossRefGoogle Scholar
  46. 46.
    Tamariz, E. and Grinnell, F. (2002) Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol. Biol. Cell 13, 3915–3929.PubMedCrossRefGoogle Scholar
  47. 47.
    Pelham, R. J. and Wang, Y-L. (1997) Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Nat. Acad. Sci. USA 94, 13661–13665.PubMedCrossRefGoogle Scholar
  48. 48.
    Wang, Y.-K., Wang, Y.-H., Wang, C.-Z., et al. (2003) Rigidity of collagen fibrils controls collagen gel-induced down-regulation of focal adhesion complex proteins mediated by α2β1 integrin. J. Biol. Chem. 278, 21886–21892.PubMedCrossRefGoogle Scholar
  49. 49.
    Semler, E. J., Lancin, P. A., Dasgupta, A., and Moghe, P. V. (2005) Engineering hepatocellular morphogenesis and function via ligand-presenting hydrogels with graded mechanical compliance. Biotechnol. Bioeng. 89, 296–307.PubMedCrossRefGoogle Scholar
  50. 50.
    Engler, A., Bacakova, L., Newman, C., Hategan, A., Griffin, M., and Discher, D. (2004) Substrate compliance versus ligand density in cell on gel responses. Biophys. J. 86, 617–628.PubMedCrossRefGoogle Scholar
  51. 51.
    Danielson, C. C. (2004) Tensile mechanical and creep properties of Descement's membrane and lens capsule. Exper. Eye. Res. 79, 343–350.CrossRefGoogle Scholar
  52. 52.
    Chen, C. S., Yannas, I. V., and Spector, M. (1995) Pore strain behaviour of collagen-glycosaminoglycan analogues of extracellular matrix. Biomaterials 16, 777–783.PubMedCrossRefGoogle Scholar
  53. 53.
    Codd, S. L., Lambert, R. K., Alley, M. R., Pack, R. J. (1994) Tensile stiffness of ovine tracheal wall. J. Appl. Physiol. 76, 2627–2635.PubMedCrossRefGoogle Scholar
  54. 54.
    Wozniak, M. A., Desai, R., Solski, P. A., Der, C. J., and Keely, P. J. (2003) ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J. Cell Biol. 163, 583–595.PubMedCrossRefGoogle Scholar
  55. 55.
    Deroanne, C. F., Lapiere, C. M., and Nusgens, B. V. (2001) In vitro tubulogenesis of endothelial cells by relaxation of the coupling extracellular matrix-cytoskeleton. Cardiovasc. Res. 49, 647–658.PubMedCrossRefGoogle Scholar
  56. 56.
    Paszek, M. J. and Weaver, V. M. (2004) The tension mounts: mechanics meets morphogenesis and malignancy. J. Mamm. Gland Biol. Neoplasia 9, 325–342.CrossRefGoogle Scholar
  57. 57.
    Gunn, J. W., Turner, S. D., and Mann, B. K. (2005) Adhesive and mechanical properties of hydrogels influence neurite extension. J. Biomed. Mater. Res. 72A, 91–97.CrossRefGoogle Scholar
  58. 58.
    Grinnell, F. (2003) Fibroblast biology in three-dimensional collagen matrices. Trends Cell. Biol. 13, 264–269.PubMedCrossRefGoogle Scholar
  59. 59.
    Mercier, I., Lechaire, J-P. Desmouliere, A., Gaill, F., and Aumailley, M. (1996) Interactions of human skin fibroblasts with monomeric or fibrillar collagens induce different organization of the cytoskeleton. Exp. Cell Res. 225, 245–256.PubMedCrossRefGoogle Scholar
  60. 60.
    Sato, K., Hattori, S., Irie, S., and Kawashima, S. (2003) Spike formation by fibroblasts adhering to fibrillar collagen I gel. Cell. Struc. Func. 28, 229–241.CrossRefGoogle Scholar
  61. 61.
    Koyama, H., Raines, E. W., Bornfeldt, K. E., Roberts, J. M., and Ross, R. (1996) Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of cdk2 inhibitors. Cell 87, 1069–1078.PubMedCrossRefGoogle Scholar
  62. 62.
    Overton, J. (1977) Response of epithelial and mesenchymal cells to culture on basement lamella observed by scanning microscopy. Exp. Cell Res. 105, 313–323.PubMedCrossRefGoogle Scholar
  63. 63.
    Meller, D., Peters, K., and Meller, K. (1997) Human cornea and sclera studied by atomic force microscopy. Cell Tiss. Res. 288, 111–118.CrossRefGoogle Scholar
  64. 64.
    Sasaki, N. and Odajima, S. (1996) Elongation mechanism of collagen fibrils and force-strain relations of tendon at each level of structural hierarchy. J. Biomech 29, 1131–1136.PubMedCrossRefGoogle Scholar
  65. 65.
    Lee, C. H., Shin, H. J., Cho, I. H., et al. (2005) Nanofiber alignment and direction of mechanical strain affect the ECM production of human AACL fibroblast. Biomaterials 26, 1261–1270.PubMedCrossRefGoogle Scholar
  66. 66.
    Nakatsuji, N. and Johnson, K. E. (1984) Experimental manipulation of a contact guidance system in amphibian gastrulation by mechanical tension. Nature 307, 453–455.PubMedCrossRefGoogle Scholar
  67. 67.
    Oakley, C., Jaeger, N. A. F., and Brunette, D. M. (1997) Sensitivity of fibroblasts and their cytoskeletons to substratum topographies: topographic guidance and topographic compensation by micromachined grooves of different dimensions. Exp. Cell Res. 234, 413–424.PubMedCrossRefGoogle Scholar
  68. 68.
    Teixeira, A. I., Abrams, G. A., Bertics, P. J., Murphy, C. J., and Nealey, P. F. (2003) Epithelial contact guidance on well-defined micro- and nanostructured substrates. J. Cell Sci. 116, 1881–1892.PubMedCrossRefGoogle Scholar
  69. 69.
    Lehnert, D., Wehrle-Haller, B., David, C., et al. (2003) Cell behaviour on micropatterned substrata: limits of extracellular matrix geometry for spreading and adhesion. J. Cell Sci. 117, 41–52.CrossRefGoogle Scholar
  70. 70.
    Dalby, M. J., Riehle, M. O., Sutherland, D. S., Agheli, H., and Curtis, A. S. G. (2004) Changes in fibroblast morphology in response to nano-columns produced by colloidal lithography. Biomaterials 25, 5415–5422.PubMedCrossRefGoogle Scholar
  71. 71.
    Dalton, B. A., Walboomers, X. F., Diziegielewski, M., et al. (2001) Modulation of epithelial tissue and cell migration by microgrooves. J. Biomed. Mater. Res. 56, 195–207.PubMedCrossRefGoogle Scholar
  72. 72.
    Wojciak-Stothard, B., Curtis, A., Monaghan, W., MacDonald, K., and Wilkinson, C. (1996) Guidance and activation of murine macrophages by nanometric scale topography. Exp. Cell Res. 223, 426–435.PubMedCrossRefGoogle Scholar
  73. 73.
    Webb, A., Clark, P., Skepper, J., Compston, A., and Wood, A. (1995) Guidance of oligodendrocytes and their progenitors by substratum topography. J. Cell Sci. 108, 2747–2760.PubMedGoogle Scholar
  74. 74.
    Saneinejad, S. and Shoichet, M. S. (2000) Patterned poly(chlorotrifluoroethylene) guides primary nerve cell adhesion and neurite outgrowth. J. Biomed. Mater. Res. 50, 465–474.PubMedCrossRefGoogle Scholar
  75. 75.
    Yang, F., Murugan, R., Wang, S., and Ramakrishna, S. (2005) Electrospinning of nano/micro scale poly(l-lactic acid) aligned fibers and their potential in neural tissue engineering. Biomaterials 26, 2603–2610.PubMedCrossRefGoogle Scholar
  76. 76.
    Geiger, B., Bershadsky, A., Pankov, R., and Yamada, K. M. (2001) Transmembrane cross-talk between the extracellular matrix-cytoskeleton. Nat. Rev. Mol. Cell. Biol. 2, 793–805.PubMedCrossRefGoogle Scholar
  77. 77.
    Hynes, R. O. (1999) The dynamic dialogue between cells and matrices: implications of fibronectin's elasticity. Proc. Natl. Acad. Sci. USA 96, 2588–2590.PubMedCrossRefGoogle Scholar
  78. 78.
    Katsumi, A., Orr, A. W., Tzima, E., and Schwartz, M. A. (2004) Integrins in mechanotransduction. J. Biol. Chem. 279, 12001–12004.PubMedCrossRefGoogle Scholar
  79. 79.
    Maheshwari, G., Brown, G., lauffenburger, D. A., Wells, A., and Griffith, L. G. (2000) Cell adhesion and motility depend on nanoscale RGD clustering. J. Cell Sci. 113, 1677–1686.PubMedGoogle Scholar
  80. 80.
    Kato, M. and Mrksich, M. (2004) The synergy peptide PHSRN and the adhesion peptide RGD mediate cell adhesion through a common mechanism. Biochem 43, 15811–15821.CrossRefGoogle Scholar
  81. 81.
    Wang, H-B., Dembo, M., and Wang Y-L. (2000) Substrate flexibility regulates growth and apoptosis of normal but not transformed cells. Am. J. Physiol. Cell Physiol. 279, C1345-C1350.PubMedGoogle Scholar
  82. 82.
    Burridge, K. and Wennerberg, K. (2004) Rho and Rac take center stage. Cell 116, 167–179.PubMedCrossRefGoogle Scholar
  83. 83.
    Nobes, C. D. and Hall, A. (1995) Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell 81, 53–62.PubMedCrossRefGoogle Scholar
  84. 84.
    Etienne-Manneville, S. and Hall, A. (2002) Rho GTPases in cell biology, Nature 420, 629–635.PubMedCrossRefGoogle Scholar
  85. 85.
    Bishop, A. L. and Hall, A. (2000) Rho GTPases and their effector proteins. Biochem. J. 348, 241–255.PubMedCrossRefGoogle Scholar
  86. 86.
    DeMali, K. A., Burridge, K. (2003) Coupling membrane protrusion and cell adhesion. J. Cell Sci. 116, 2389–2397.PubMedCrossRefGoogle Scholar
  87. 87.
    Connolly, J. O., Simpson, N., Hewlett, L., and Hall A. (2002) Rac regulates endothelial morphogenesis and capillary assembly. Mol. Biol. Cell 13, 2474–2485.PubMedCrossRefGoogle Scholar
  88. 88.
    Sander, E., ten Klooster, J. P., van Delft, S., van der Kammen, R. A., and Collard, J. G. (1999) Rac downregulates Rho activity: reciprocal balance between both GTPases determines cellular morphology and migratory behavior. J. Cell Biol. 147, 1009–1021.PubMedCrossRefGoogle Scholar
  89. 89.
    Zhou, H. and Kramer, R. H. (2004) Integrin engagement differentially modulates epithelial cell motility by RhoA/ROCK and PAK1. J. Biol. Chem. 205, 10624–10635.Google Scholar
  90. 90.
    Tsuji, T., Ishizaki, T., Okamoto, M., et al. (2002) ROCK and mDiaA1 antagonize in Rho-dependent Rac activation in Swiss 3T3 fibroblasts. J. Cell Biol. 157, 819–830.PubMedCrossRefGoogle Scholar
  91. 91.
    Watanabe, N., Kato, T., Fujita, A., Ishizaki, T., and Narumiya, S. (1999) Cooperation between mDia1 and ROCK in Rho-induced actin reorganization. Nat. Cell Biol. 1, 136–143.PubMedCrossRefGoogle Scholar
  92. 92.
    Baneyx, G., Baugh, L., and Vogel, V., (2002) Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension. Proc. Natl. Acad. Sci. USA 99, 5139–5143.PubMedCrossRefGoogle Scholar
  93. 93.
    Kale, S., Biermann, S., Edwards, C., Tarnowski, C., Morris, M., and Long, M. W. (2000) Three-dimensional cellular development is essential for ex vivo formation of human bone. Nat. Biotech. 18, 954–958.CrossRefGoogle Scholar
  94. 94.
    Li, S., Lao, J., Chen, B. P. C., et al. (2003) Genomic analysis of smooth muscle cells in 3-dimensional collagen matrix. FASEB J. 17, 97–99.PubMedCrossRefGoogle Scholar
  95. 95.
    Hanssen, E., Reinboth, B., and Gibson, M. A. (2003) Covalent and non-covalent interactions of betaig-h3 with collagen IV. Bet ig-h3 is covalently attached to the aminoterminal region of collagen IV in tissue microfibrils. J. Biol. Chem. 278, 24334–24441.PubMedCrossRefGoogle Scholar
  96. 96.
    Hubbell, J. A. (2003) Materials as morphogenetic guides in tissue engineering. Curr. Opin. Biotech. 14, 551–558.PubMedCrossRefGoogle Scholar
  97. 97.
    Szklarcyzk, A., Lapinkska, J., Rylski, M., McKay, R. D., and Kaczmarek, L. (2002) Matrix metalloproteinase-9 undergoes expression and activation during dendritic remodeling in adult hippocampus. J. Neurosci. 22, 920–930.Google Scholar
  98. 98.
    Lemons, M. L., Sandy, J. D., Anderson, D. K., and Howland, D. R. (2003) Intact aggregan and chondroitin sulfate-depleted aggrecan core glycoprotein inhibit axon growth in the adult rat spinal cord. Exp. Neurol. 184, 981–990.PubMedCrossRefGoogle Scholar
  99. 99.
    Genove, E., Shen, C., Zhang, S., and Semino, C. E. (2005) The effect of functionalized self-assembling peptide scaffolds on human aortic endothelial cell function. Biomaterials 26, 3341–3351.PubMedCrossRefGoogle Scholar
  100. 100.
    Silva, G. A., Czeisler, C., Niece, K. L., Harrington, D., Kessler, J., and Stupp, S. I. (2004) Selective differentiation of neuronal progenitor cells by high epitope density nanofibers. Science 303, 1352–1355.PubMedCrossRefGoogle Scholar
  101. 101.
    Zhang, S., Holmes, T. C., DiPersio, C. M., Hynes, R. O., Su, X., and Rich, A. (1995) Self-complementary oligopeptide matrices support mammalian cell attachment. Biomaterials 16, 1385–1393.PubMedCrossRefGoogle Scholar
  102. 102.
    Ryadnov, M. G. and Woolfson, D. N. (2003) Engineering the morphology of a self-assembling protein fibre. Nat. Mater. 2, 329–332.PubMedCrossRefGoogle Scholar
  103. 103.
    Zhang, S. (2003) Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotech. 21, 1171–1177.CrossRefGoogle Scholar
  104. 104.
    Smith, L. A. and Ma, P. X. (2004) Nan-fibrous scaffolds for tissue engineering. Colloids Surfaces B: Biointerfaces 39, 125–131.Google Scholar
  105. 105.
    Chung, H. Y., Hal, J. R. B., Gogins, M. A., Crofoot, D. G., and Weik, T. M. (2004) Polymer, polymer microfiber, polymer nanofiber and applications including filter structures. US Patent No. 6,743,273 B2Google Scholar
  106. 106.
    Doshi, J. and Reneker, G. L. (1995) Electrospinning process and applications of electrospun fibers. J. Electrost. 35, 151–160.CrossRefGoogle Scholar
  107. 107.
    Schindler, M., Ahmed, I., Nur-E-Kamal, A., et al. (2005) Synthetic nanofibrillar matrix promotes in vivo-like organization and morphogenesis for cells in culture. Biomaterials, 26, 5624–5631.PubMedCrossRefGoogle Scholar
  108. 108.
    Nur-E-Kamal, A., Ahmed, I., Kamal, J., Schindler, M., and Meiners, S. (2005) Three dimensional nanofibrillar surfaces induce activation of Rac. Biochem. Biophys. Res. Commun. 331, 428–34.PubMedCrossRefGoogle Scholar
  109. 109.
    Li, W. J., Danielson, K. G., Alexander, P. G., and Tuan, R. S. (2003) Biological response of chondrocytes cultured in three-dimensional nanofibrous poly(epsilon-caprolactone) scaffolds. J. Biomed. Mater. Res. 67A, 1105–1114.CrossRefGoogle Scholar
  110. 110.
    Yoshimoto, H., Shin, Y. M., Terai, H., and Vacanti, J. P. (2003) A biodegradable nanofiber scaffold by electrospinning and its potential for bone tissue engineering. Biomaterials 12, 2077–2082.CrossRefGoogle Scholar
  111. 111.
    Boland, E. D., Matthews, J. A., Pawlowski, K. J., Simpson, D. G., Wnek, G. E., and Bowlin, G. L. (2004) Electrospinning collagen and elastin: preliminary vascular tissue engineering. Front. Biosci. 9, 1422–1432.PubMedGoogle Scholar
  112. 112.
    Li, M., Mondrinos, M. J., Gandhi, M. R., Ko, F. K., Weiss, A. S., and Lelkes, P. I. (2005) Electrospun protein fibers as matrices for tissue engineering. Biomaterials 26, 5999–6008.PubMedCrossRefGoogle Scholar
  113. 113.
    Stankus, J. J., Guan, J., and Wagner, W. R. (2004) Fabrication of biodegradable elastomeric scaffolds with sub-micron morphologies. J. Biomed. Mater. Res. 70A, 603–614.CrossRefGoogle Scholar
  114. 114.
    Lee, P. H., Trowbridge, J. M., Taylor, K. R., Morhenn, V. B., and Gallo, R. L. (2004) Dermatan sulfate proteoglycan and glycosaminoglycan synthesis is induced in fibroblasts by transfer to a three-dimensional extracellular environment. J. Biol. Chem. 279, 48640–48646.PubMedCrossRefGoogle Scholar
  115. 115.
    Frondoza, C., Sohrabi, A., and Hungerford, D. (1996) Human chondrocytes proliferate and produce matrix components in microcarrier suspension culture. Biomaterials 17, 879–888.PubMedCrossRefGoogle Scholar
  116. 116.
    Overstreet, M., Sohrabi, A., Polotsky, A., Hungerford, D. S., and Frondoza, C. (2003) Collagen microcarrier spinner culture promotes osteoblast proliferation and synthesis of matrix proteins. In Vitro Cell. Dev. Biol. Anim. 39, 228–234.PubMedCrossRefGoogle Scholar
  117. 117.
    Hayashi, S., Osawa, T., and Tohyama, K. (2002) Comparative observations on corneas, with special reference to Bowman's layer and Descemet's membrane in mammals and amphibians. J. Morphol. 254, 247–258.PubMedCrossRefGoogle Scholar
  118. 118.
    Wolf, K., Muller, R., Borgmann, S., Brocker, E.-B., and Friedl, P. (2003) Amoeboid shape change and contact guidance: T-lymphocyte crawling through fibrillar collagen is independent of matrix remodeling by MMPs and other proteases. Blood 102, 3262–3269.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2006

Authors and Affiliations

  • Melvin Schindler
    • 1
  • Alam Nur-E-Kamal
    • 2
  • Ijaz Ahmed
    • 2
  • Jabeen Kamal
    • 2
  • Hsing-Yin Liu
    • 2
  • Nathan Amor
    • 2
  • Abdul S. Ponery
    • 2
  • David P. Crockett
    • 3
  • Timothy H. Grafe
    • 4
  • H. Young Chung
    • 4
  • Thom Weik
    • 4
  • Elizabeth Jones
    • 4
  • Sally Meiners
    • 2
  1. 1.Department of Biochemistry and Molecular BiologyMichigan State UniversityEast Lansing
  2. 2.Department of PharmacologyUMDNJ-Robert Wood Johnson Medical SchoolPiscataway
  3. 3.Dept. of Neurosciences and Cell BiologyUMDNJ-Robert Wood Johnson Medical SchoolPiscataway
  4. 4.Donaldson Co., Inc.Minneapolis

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