Abstract
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.
Similar content being viewed by others
References
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Walpita, D. and Hay, E. (2002) Studying actin-dependent processes in tissue culture. Nat. Rev. Mol. Rev. Mol. Cell Biol. 3, 137–141.
Mueller-Klieser, W. (1997) Three dimensional cell cultures: from molecular mechanisms to clinical applications. Am. J. Physiol. (Cell Physiol.) 42, C1109-C1123.
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.
Abbott, A. (2003) Cell culture: biology's new dimension. Nature 424, 870–872.
Kalluri, R. (2003) Basement membranes: structure, assembly and role in tumour angiogenesis. Nat. Rev. Cancer 3, 422–433.
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.
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.
Boudreau, N. J. (2003) Organized living: from cell surfaces to basement membranes. Sci. STKE 196, pe34.
Miner, J. H. and Yurchenco, P. D. (2004) Laminin functions in tissue morphogenesis. Annu. Rev. Cell Dev. Biol. 20, 255–284.
Michelacci, Y. M. (2003) Collagens and proteoglycans of the corneal extracellular matrix. Braz. J. Med. Biol. Res. 36, 1037–1046.
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.
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.
Schmeichel, K. L. and Bissell, M. J. (2003) Modeling tissue-specific signaling and organ function in three dimensions. J. Cell. Sci. 116, 2377–2388.
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.
Kleinman, H. K., Philp, D., and Hoffman, M. P. (2003) Role of the extracellular matrix in morphogenesis. Curr. Op. Biotech. 14, 526–532.
Cukierman, E., Pankov, R., Stevens, D. R., and Yamada, K. M. (2001) Taking cell-matrix adhesions to the third dimension. Science 294, 1708–1712.
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.
Cukierman, E., Pankov, R., and Yamada, K. M. (2002) Cell interactions with three-dimensional matrices. Curr. Opin. Cell. Biol. 14, 633–639.
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.
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.
Shin, H., Jo, S., and Mikos, A. G. (2003) Biomimetic materials for tissue engineering. Biomaterials 24, 4353–4364.
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.
Zamir, E. and Geiger, B. (2001) Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 14, 3583–3590.
Wozniak, M. A., Modzelewska, K., Kwong, L., and Keely, P. (2004) Focal adhesion regulation of cell behavior. Biochim. Biophys. Acta. 1692, 103–119.
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.
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.
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.
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.
Balis, F. M. (2002) Evolution of anticancer drug discovery and the role of cell-based screening. J. Natl. Cancer Inst. 94, 78–79.
Friedl, P. (2004) Prespecification and plasticity: shifting mechanisms of cell migration. Curr. Op. Cell. Biol. 16, 14–23.
Lauffenburger, D. A. and Horwitz, A. F. (1996) Cell migration: a physically integrated molecular process. Cell 84, 359–369.
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.
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.
Condeelis, J. and Segall, J. E. (2003) Intravital imaging of cell movement in tumours. Nat. Rev. Cancer 3, 921–930.
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.
Tamariz, E. and Grinnell, F. (2002) Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol. Biol. Cell 13, 3915–3929.
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.
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.
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.
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.
Danielson, C. C. (2004) Tensile mechanical and creep properties of Descement's membrane and lens capsule. Exper. Eye. Res. 79, 343–350.
Chen, C. S., Yannas, I. V., and Spector, M. (1995) Pore strain behaviour of collagen-glycosaminoglycan analogues of extracellular matrix. Biomaterials 16, 777–783.
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.
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.
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.
Paszek, M. J. and Weaver, V. M. (2004) The tension mounts: mechanics meets morphogenesis and malignancy. J. Mamm. Gland Biol. Neoplasia 9, 325–342.
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.
Grinnell, F. (2003) Fibroblast biology in three-dimensional collagen matrices. Trends Cell. Biol. 13, 264–269.
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.
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.
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.
Overton, J. (1977) Response of epithelial and mesenchymal cells to culture on basement lamella observed by scanning microscopy. Exp. Cell Res. 105, 313–323.
Meller, D., Peters, K., and Meller, K. (1997) Human cornea and sclera studied by atomic force microscopy. Cell Tiss. Res. 288, 111–118.
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.
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.
Nakatsuji, N. and Johnson, K. E. (1984) Experimental manipulation of a contact guidance system in amphibian gastrulation by mechanical tension. Nature 307, 453–455.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hynes, R. O. (1999) The dynamic dialogue between cells and matrices: implications of fibronectin's elasticity. Proc. Natl. Acad. Sci. USA 96, 2588–2590.
Katsumi, A., Orr, A. W., Tzima, E., and Schwartz, M. A. (2004) Integrins in mechanotransduction. J. Biol. Chem. 279, 12001–12004.
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.
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.
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.
Burridge, K. and Wennerberg, K. (2004) Rho and Rac take center stage. Cell 116, 167–179.
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.
Etienne-Manneville, S. and Hall, A. (2002) Rho GTPases in cell biology, Nature 420, 629–635.
Bishop, A. L. and Hall, A. (2000) Rho GTPases and their effector proteins. Biochem. J. 348, 241–255.
DeMali, K. A., Burridge, K. (2003) Coupling membrane protrusion and cell adhesion. J. Cell Sci. 116, 2389–2397.
Connolly, J. O., Simpson, N., Hewlett, L., and Hall A. (2002) Rac regulates endothelial morphogenesis and capillary assembly. Mol. Biol. Cell 13, 2474–2485.
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.
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.
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.
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.
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.
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.
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.
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.
Hubbell, J. A. (2003) Materials as morphogenetic guides in tissue engineering. Curr. Opin. Biotech. 14, 551–558.
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.
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.
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.
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.
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.
Ryadnov, M. G. and Woolfson, D. N. (2003) Engineering the morphology of a self-assembling protein fibre. Nat. Mater. 2, 329–332.
Zhang, S. (2003) Fabrication of novel biomaterials through molecular self-assembly. Nat. Biotech. 21, 1171–1177.
Smith, L. A. and Ma, P. X. (2004) Nan-fibrous scaffolds for tissue engineering. Colloids Surfaces B: Biointerfaces 39, 125–131.
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 B2
Doshi, J. and Reneker, G. L. (1995) Electrospinning process and applications of electrospun fibers. J. Electrost. 35, 151–160.
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.
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.
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.
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.
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.
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.
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.
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.
Frondoza, C., Sohrabi, A., and Hungerford, D. (1996) Human chondrocytes proliferate and produce matrix components in microcarrier suspension culture. Biomaterials 17, 879–888.
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.
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.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schindler, M., Nur-E-Kamal, A., Ahmed, I. et al. Living in three dimensions. Cell Biochem Biophys 45, 215–227 (2006). https://doi.org/10.1385/CBB:45:2:215
Issue Date:
DOI: https://doi.org/10.1385/CBB:45:2:215