Annals of Biomedical Engineering

, Volume 33, Issue 11, pp 1469–1490

Mechanobiology in the Third Dimension



Cells are mechanically coupled to their extracellular environments, which play critical roles in both communicating the state of the mechanical environment to the cell as well as in mediating cellular response to a variety of stimuli. Along with the molecular composition and mechanical properties of the extracellular matrix (ECM), recent work has demonstrated the importance of dimensionality in cell-ECM associations for controlling the sensitive communication between cells and the ECM. Matrix forces are generally transmitted to cells differently when the cells are on two-dimensional (2D) vs. within three-dimensional (3D) matrices, and cells in 3D environments may experience mechanical signaling that is unique vis-à-vis cells in 2D environments, such as the recently described 3D-matrix adhesion assemblies. This review examines how the dimensionality of the extracellular environment can affect in vitro cell mechanobiology, focusing on collagen and fibrin systems.

Key Words

Cell mechanics Tissue mechanics Collagen Fibrin Tissue engineering Hydrogel Fibroblast Stress shielding Cell strain 


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  1. 1.
    Agoram, B., and V. H. Barocas. Coupled macroscopic and microscopic scale modeling of fibrillar tissues and tissue equivalents. J. Biomech. Eng. 123:362–369, 2001.CrossRefGoogle Scholar
  2. 2.
    Allen, T. D., S. L. Schor, and A. M. Schor. An ultrastructural review of collagen gels, a model system for cell matrix, cell-basement membrane and cell-cell interactions. Scan. Electron Microsc. 1984(I):375–390, 1984.Google Scholar
  3. 3.
    Altman, G. H., R. L. Horan, I. Martin, J. Farhadi, P. R. H. Stark, J. C. R. Volloch, G. Vunjak-Novakovic, and D. L. Kaplan. Cell differentiation by mechanical stress. FASEB J. Online December 28, 2001, doi: 10.1096/fj.01-0656fje, 2001.Google Scholar
  4. 4.
    Anand, S., J.-H. Wu, and S. L. Diamond. Enzyme-mediated proteolysis of fibrous biopolymers: Dissolution front movement in fibrin or collagen under conditions of diffusive or convective transport. Biotechnol. Bioeng. 48:89–107, 1995.CrossRefGoogle Scholar
  5. 5.
    Arnaout, M. A., S. L. Goodman, and J.-P. Xiong. Coming to grips with integrin binding to ligands. Curr. Opin. Cell Biol. 14:641–651, 2002.CrossRefGoogle Scholar
  6. 6.
    Arora, P. D., N. Narani, and C. A. G. McCulloch. The compliance of collagen gels regulates transforming growth factor-β induction of α-smooth muscle actin in fibroblasts. Am. J. Pathol. 154:871–882, 1999.Google Scholar
  7. 7.
    Avila, J., and J. D. Nido. Control of microtubule polymerization and stability. In: The Cytoskeleton: Structure and Assembly, edited by J. E. Hekseth and I. F. Pryme, Vol. 1. Greenwich: JAI Press, 1995, pp. 47–85.Google Scholar
  8. 8.
    Bailey, M., H. Xiao, M. Ogle, and N. Vyavahare. Aluminum chloride pretreatment of elastin inhibits elastolysis by matrix metalloproteinases and leads to inhibition of elastin-oriented calcification. Am. J. Pathol. 159:1981–1986, 2001.Google Scholar
  9. 9.
    Balaban, N. Q., U. S. Schwarz, D. Riveline, P. Goichberg, G. Tzur, I. Sabanay, D. Mahalu, S. Safran, A. Bershadsky, L. Addadi, and B. Geiger. Force and focal adhesion assembly: A close relationship studied using elastic micropatterned substrates. Nature Cell Biol. 3:466–472, 2001.CrossRefGoogle Scholar
  10. 10.
    Bale, M. D., M. F. Müller, and J. D. Ferry. Rheological studies of creep and creep recovery of unligated fibrin clots: Comparison of clots prepared with thrombin and ancrod. Biopolymers 24:461–482, 1985.CrossRefGoogle Scholar
  11. 11.
    Ballestrem, C., B. Wehrle-Haller, and B. A. Imhof. Actin dynamics in living mammalian cells. J. Cell Sci. 111:1649–1658, 1998.Google Scholar
  12. 12.
    Barbee, K. A., P. F. Davies, and R. Lal. Shear stress-induced reorganization of the surface topography of living endothelial cells imaged by atomic force microscopy. Circ. Res. 74:163–171, 1994.Google Scholar
  13. 13.
    Barocas, V. H., A. G. Moon, and R. T. Tranquillo. The fibroblast-populated collagen microsphere assay of cell traction force: Part 2. Measurement of the cell traction parameter. J. Biomech. Eng. 117:161–170, 1995.Google Scholar
  14. 14.
    Barocas, V. H., and R. T. Tranquillo. An anisotropic biphasic theory of tissue-equivalent mechanics: The interplay among cell traction, fibrillar network deformation, fibril alignment, and cell contact guidance. J. Biomech. Eng. 119:137–145, 1997.Google Scholar
  15. 15.
    Barry, S. T., and D. R. Critchley. The RhoA-dependent assembly of focal adhesions in Swiss 3T3 cells is associated with increased tyrosine phosphorylation and the recruitment of both pp125FAK and protein kinase C-δ to focal adhesions. J. Cell Sci. 107:2033–2045, 1994.Google Scholar
  16. 16.
    Bell, E., B. Ivarsson, and C. Merrill. Production of a tissue-like structure by contraction of collagen lattices by human fibroblasts of different proliferative potential in vitro. Proc. Natl. Acad. Sci. U.S.A. 76:1274–1278, 1979.Google Scholar
  17. 17.
    Bellows, C. G., A. H. Melcher, and J. E. Aubin. Association between tension and orientation of periodontal ligament fibroblasts and exogenous collagen fibres in vitro. J. Cell Sci. 58:125–138, 1982.Google Scholar
  18. 18.
    Birk, D. E., and R. L. Trelstad. Extracellular compartments in matrix morphogenesis—Collagen fibril, bundle, and lamellar formation by corneal fibroblasts. J. Cell Biol. 99:2024–2033, 1984.CrossRefGoogle Scholar
  19. 19.
    Bissell, M. J., D. C. Radisky, A. Rizki, V. M. Weaver, and O. W. Petersen. The organizing principle: Microenvironmental influences in the normal and malignant breast. Differentiation 70:537–546, 2002.Google Scholar
  20. 20.
    Blombäck, B., K. Carlsson, B. Hessel, A. Liljeborg, R. Procyk, and N. Åslund. Native fibrin gel networks observed by 3D microscopy, permeation and turbidity. Biochim. Biophys. Acta 997:96–110, 1989.Google Scholar
  21. 21.
    Boardman, K. C., and M. A. Swartz. Interstitial flow as a guide for lymphangiogenesis. Circ. Res. 92:801–808, 2003.CrossRefGoogle Scholar
  22. 22.
    Bollard, T. D., L. Blanchoin, and R. D. Mullins. Molecular mechanism controlling actin filament dynamics in nonmuscle cells. Annu. Rev. Biophys. Biomol. Struct. 29:545–576, 2000.Google Scholar
  23. 23.
    Bornstein, P., and E. H. Sage. Matricellular proteins: Extracellular modulators of cell function. Curr. Opin. Cell Biol. 14:608–616, 2002.CrossRefGoogle Scholar
  24. 24.
    Brightman, A. O., B. P. Rajwa, J. E. Sturgis, M. E. McCallister, J. P. Robinson, and S. L. Voytik-Harbin. Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro. Biopolymers 54:222–234, 2000.CrossRefGoogle Scholar
  25. 25.
    Brock, A., E. Chang, C.-C. Ho, et al. Geometric determinants of directional cell motility revealed using microcontact printing. Langmuir 19:1611–1617, 2003.Google Scholar
  26. 26.
    Bromberek, B. A., P. A. J. Enever, D. I. Shreiber, M. D. Caldwell, and R. T. Tranquillo. Macrophages influence a competition of contact guidance and chemotaxis for fibroblast alignment in a fibrin gel coculture assay. Exp. Cell Res. 275:230–242, 2002.CrossRefGoogle Scholar
  27. 27.
    Brown, A. F. Neutrophil granulocytes: Adhesion and locomotion on collagen substrata and in collagen matrices. J. Cell Sci. 58:455–467, 1982.Google Scholar
  28. 28.
    Brown, R. A., R. Prajapati, D. A. McGrouther, I. V. Yannas, and M. Eastwood. Tensional homeostasis in dermal fibroblasts: Mechanical responses to mechanical loading in three-dimensional substrates. J. Cell. Physiol. 175:323–332, 1998.CrossRefGoogle Scholar
  29. 29.
    Burghardt, W. R., T. K. Goldstick, J. Leneschmidt, and K. Kempka. Nonlinear viscoelasticity and the thrombelastograph: 1. Studies on bovine plasma clots. Biorheol. 32:621–630, 1995.Google Scholar
  30. 30.
    Burridge, K. Are stress fibres contractile? Nature 294:691–692, 1981.Google Scholar
  31. 31.
    Butler, P. J., G. Norwich, S. Weinbaum, and S. Chien. Shear stress induces a time- and position dependent increase in endothelial cell membrane fluidity. Am. J. Physiol. Cell Physiol. 280:C962–C969, 2001.Google Scholar
  32. 32.
    Butler, J. P., I. M. Tolic-Nø rrelykke, B. Fabry, and J. J. Fredberg. Traction fields, moments, and strain energy that cells exert on their surroundings. Am. J. Physiol. Cell Physiol. 282:C595–C605, 2002.Google Scholar
  33. 33.
    Chalfie, M., Y. Tu, G. Euskirchen, W. W. Ward, and D. C. Prasher. Green fluorescent protein as a marker for gene expression. Science 263:802–805, 1994.Google Scholar
  34. 34.
    Chandran, P. L., and V. H. Barocas. Microstructural mechanics of collagen gels in confined compression: Poroelasticitsy, viscoelasticity, and collapse. J. Biomech. Eng. 126:152–166, 2004.CrossRefGoogle Scholar
  35. 35.
    Chandran, P. L. and V. H. Barocas. Affine vs. non-affine fibril kinematics in collagen networks: Theoretical studies of network behavior. J. Biomech. Eng. 2005, in press.Google Scholar
  36. 36.
    Chen, C. S., M. Mrksich, S. Huang, G. M. Whitesides, and D. E. Ingber. Geometric control of cell life and death. Science 276:1425–1428, 1997.Google Scholar
  37. 37.
    Choe, M. M.-H, P. H. S. Sporn, and M. A. Swartz. An in vitro airway wall model of remodeling. Am. J. Physiol. Lung Cell. Mol. Physiol. 285:L427–L433, 2003.Google Scholar
  38. 38.
    Choquet, D., D. P. Felsenfeld, and M. P. Sheetz. Extracellular matrix rigidity causes strengthening of integrin–cytoskeleton linkages. Cell 88:39–48, 1997.CrossRefGoogle Scholar
  39. 39.
    Christensen, R. M., and F. M. Waals. Effective stiffness of randomly oriented fibre composites. J. Composite Mater. 6:518–532, 1972.Google Scholar
  40. 40.
    Ciano, P. S., R. B. Colvin, A. M. Dvorak, J. McDonagh, and H. F. Dvorak. Macrophage migration in fibrin gel matrices. Lab. Invest. 54:62–70, 1986.Google Scholar
  41. 41.
    Costa, K. D., W. J. Hucker, and F. C.-P. Yin. Buckling of actin stress fibers: A new wrinkle in the cytoskeletal tapestry. Cell Motil. Cytoskeleton 52:266–274, 2002.CrossRefGoogle Scholar
  42. 42.
    Couchman, J. R., and D. A. Rees. The behaviour of fibroblasts migrating from chick heart explants: Changes in adhesion, locomotion and growth, and in the distribution of actomyosin and fibronectin. J. Cell Sci. 39:149–165, 1979.Google Scholar
  43. 43.
    Cowin, S. C. The mechanical and stress adaptive properties of bone. Ann. Biomed. Eng. 11:263–295, 1983.Google Scholar
  44. 44.
    Cox, H. L. The elasticity and strength of paper and other fibrous materials. Br. J. Appl. Phys. 3:72–79, 1952.Google Scholar
  45. 45.
    Crevensten, G., A. J. L. Walsh, D. Ananthakrishnan, et al. Intervertebral disc cell therapy for regeneration: Mesenchymal stem cell implantation in rat intervertebral discs. Ann. Biomed. Eng. 32:430–434, 2004.Google Scholar
  46. 46.
    Cukierman, E., R. Pankov, and K. M. Yamada. Cell interactions with three-dimensional matrices. Curr. Opin. Cell Biol. 14:633–639, 2002.CrossRefGoogle Scholar
  47. 47.
    Cukierman, E., R. Pankov, D. R. Stevens, and K. M. Yamada. Taking cell–matrix adhesions to the third dimension. Science 294:1708–1712, 2001.CrossRefGoogle Scholar
  48. 48.
    Dalby, M. J., M. O. Riehle, S. J. Yarwood, C. D. W. Wilkinson, and A. S. G. Curtisa. Nucleus alignment and cell signaling in fibroblasts: Response to a micro-grooved topography. Exp. Cell Res. 284:274–282, 2003.CrossRefGoogle Scholar
  49. 49.
    Davies, P. F., J. Zilberberg, and B. P. Helmke. Spatial microstimuli in endothelial mechanosignaling. Circ. Res. 92:359–370, 2003.CrossRefGoogle Scholar
  50. 50.
    Delacourt, C., P.-H. Jarraeu, and J. Bourbon. Développement alvéolaire normal et pathologique [French]. Rev. Mal. Respir. 20:373–383, 2003.Google Scholar
  51. 51.
    Dubey, N., P. C. Letourneau, and R. T. Tranquillo. Guided neurite elongation and Schwann cell invasion into magnetically aligned collagen in simulated peripheral nerve regeneration. Exp. Neurol. 158:338–350, 1999.CrossRefGoogle Scholar
  52. 52.
    Dvorak, H. F. Tumors: Wounds that do not heal. N. Engl. J. Med. 315:1650–1659, 1986.Google Scholar
  53. 53.
    Eastwood, M., D. A. McGrouther, and R. A. Brown. A culture force monitor for measurement of contraction forces generated in human dermal fibroblast cultures: Evidence for cell-matrix mechanical signalling. Biochim. Biophys. Acta 1201:186–192, 1994.Google Scholar
  54. 54.
    Eastwood, M., V. C. Mudera, D. A. McGrouther, and R. A. Brown. Effect of precise mechanical loading on fibroblast populated collagen lattices: Morphological changes. Cell Motil. Cytoskeleton 40:13–21, 1998.CrossRefGoogle Scholar
  55. 55.
    Ehrlich, H. P., and J. B. M. Rajaratnam. Cell locomotion forces versus cell contraction forces for collagen lattice contraction—An in vitro model of wound contraction. Tissue Cell 22:407–417, 1990.CrossRefGoogle Scholar
  56. 56.
    Ehrmann, R. L., and G. O. Gey. The growth of cells on a transparent gel of reconstituted rat-tail collagen. J. Natl. Cancer Inst. 16:1375–1403, 1956.Google Scholar
  57. 57.
    Elsdale, T., and J. Bard. Collagen substrata for studies on cell behavior. J. Cell Biol. 54:626–637, 1972.CrossRefGoogle Scholar
  58. 58.
    Engler, A., L. Bacakova, C. Newman, A. Hategan, M. Griffin, and D. Discher. Substrate compliance versus ligand density in cell on gel responses. Biophys. J. 86:617–628, 2004.Google Scholar
  59. 59.
    Entschladen, F., B. Niggemann, K. S. Zänker, and P. Friedl. Differential requirement of protein tyrosine kinases and protein kinase C in the regulation of T cell locomotion in three-dimensional collagen matrices. J. Immunol. 159:3203–3210, 1997.Google Scholar
  60. 60.
    Estes, B. T., J. M. Gimble, and F. Guilak. Mechanical signals as regulators of stem cell fate. Curr. Top. Dev. Biol. 60:91–126, 2004.Google Scholar
  61. 61.
    Etienne-Manneville, S. Actin and microtubules in cell motility: Which one is in control? Traffic 5:470–477, 2004.CrossRefGoogle Scholar
  62. 62.
    Fairbrother, W. J., M. A. Champe, H. W. Christinger, B. A. Keyt, and M. A. Starovasnik. Solution structure of the heparin-binding domain of vascular endothelial growth factor. Structure 6:637–648, 1998.CrossRefGoogle Scholar
  63. 63.
    Fannon, M., K. E. Forsten, and M. A. Nugent. Potentiation and inhibition of bFGF binding by heparin: A model for regulation of cellular response. Biochemistry 39:1434–1445, 2000.CrossRefGoogle Scholar
  64. 64.
    Fanti, L. A., and E. D. Glandt. Partitioning of spherical particles into fibrous matrices: 1. Density-functional theory. J. Colloid Interface Sci. 135:385–395, 1990.Google Scholar
  65. 65.
    Farquhar, T., P. R. Dawson, and P. A. Torzilli. A microstructural model for the anisotropic drained stiffness of articular-cartilage. J. Biomech. Eng. 112:414–425, 1990.Google Scholar
  66. 66.
    Flanagan, L. A., Y.-E. Ju, B. Marg, M. Osterfield, and P. A. Janmey. Neurite branching on deformable substrates. Neuroreport 13:2411–2415, 2002.Google Scholar
  67. 67.
    Forgacs, G., S. A. Newman, B. Hinner, C. W. Maier, and E. Sackmann. Assembly of collagen matrices as a phase transition revealed by structural and rheological studies. Biophys. J. 84:1272–1280, 2003.Google Scholar
  68. 68.
    Friedl, P., and E.-B. Bröcker. The biology of cell locomotion within three-dimensional extracellular matrix. Cell. Mol. Life Sci. 57:41–64, 2000.Google Scholar
  69. 69.
    Friedl, P., and E.-B. Bröcker. Biological confocal reflection microscopy: Reconstruction of three-dimensional extracellular matrix, cell migration, and matrix reorganization. In: Image Analysis: Methods and Applications, edited by D.-P. Häder, 2nd ed. Boca Raton, FL: CRC Press, 2001.Google Scholar
  70. 70.
    Friedl, P., F. Entschladen, C. Conrad, B. Niggemann, and K. S. Zänker. CD4+ T lymphocytes migrating in three-dimensional collagen lattices lack focal adhesions and utilize β1 integrin-independent strategies for polarization, interaction with collagen fibers and locomotion. Eur. J. Immunol. 28:2331–2343, 1998.CrossRefGoogle Scholar
  71. 71.
    Friedl, P., K. Maaser, C. E. Klein, B. Niggemann, G. Krohne, and K. S. Zänker. Migration of highly aggressive MV3 melanoma cells in 3-dimensional collagen lattices results in local matrix reorganization and shedding of α2 and β1 integrins and CD44. Cancer Res. 57:2061–2070, 1997.Google Scholar
  72. 72.
    Friedl, P., K. S. Zänker, and E. B. Bröcker. Cell migration strategies in 3D-extracellular matrix: Differencess in morphology, cell matrix interactions and integrin function. Microsc. Res. Tech. 43:369–378, 1998.CrossRefGoogle Scholar
  73. 73.
    Galbraith, C. G., and M. P. Sheetz. A micromachined device provides a new bend on fibroblast traction forces. Proc. Natl. Acad. Sci. U.S.A. 94:9114–9118, 1997.CrossRefGoogle Scholar
  74. 74.
    Galbraith, C. G., and M. P. Sheetz. Keratocytes pull with similar forces on their dorsal and ventral surfaces. J. Cell Biol. 147:1313–1323, 1999.CrossRefGoogle Scholar
  75. 75.
    Garcia, A. M., M. W. Lark, S. B. Trippel, and A. J. Grodzinsky. Transport of tissue inhibitor of metalloproteinases-1 through cartilage: Contributions of fluid flow and electrical migration. J. Orthop. Res. 16:734–742, 1998.CrossRefGoogle Scholar
  76. 76.
    Gardel, M. L., J. H. Shin, F. C. MacKintosh, L. Mahadevan, P. Matsudaira, and D. A. Weitz. Elastic behavior of cross-linked and bundled actin networks. Science 304:1301–1305, 2004.CrossRefGoogle Scholar
  77. 77.
    Gelse, K., E. Pöschl, and T. Aigner. Collagens—Structure, function, and biosynthesis. Adv. Drug Delivery Rev. 55:1531–1546, 2003.CrossRefGoogle Scholar
  78. 78.
    Girton, T. S., V. H. Barocas, and R. T. Tranquillo. Confined compression of a tissue-equivalent: Collagen fibril and cell alignment in response to anisotropic strain. J. Biomech. Eng. 124:568–575, 2002.CrossRefGoogle Scholar
  79. 79.
    Girton, T. S., T. R. Oegema, and R. T. Tranquillo. Exploiting glycation to stiffen and strengthen tissue equivalents for tissue engineering. J. Biomed. Mater. Res. 46:87–92, 1999.CrossRefGoogle Scholar
  80. 80.
    Grinnell, F. Fibroblasts, myofibroblasts, and wound contraction. J. Cell Biol. 124:401–404, 1994.CrossRefGoogle Scholar
  81. 81.
    Grinnell, F. Fibroblast biology in three-dimensional collagen matrices. Trends Cell Biol. 13:264–269, 2003.CrossRefGoogle Scholar
  82. 82.
    Grinnell, F., C. H. Ho, Y.-C. Lin, and G. Skuta. Differences in the regulation of fibroblast contraction of floating versus stressed collagen matrices. J. Biol. Chem. 274:918–923, 1999.CrossRefGoogle Scholar
  83. 83.
    Grodzinsky, A. J., M. E. Levenston, M. Jin, and E. H. Frank. Cartilage tissue remodeling in response to mechanical forces. Ann. Rev. Biomed. Eng. 2:691–713, 2000.CrossRefGoogle Scholar
  84. 84.
    Guidry, C., and F. Grinnell. Studies on the mechanism of hydrated collagen gel reorganization by human skin fibroblasts. J. Cell Sci. 79:67–81, 1985.Google Scholar
  85. 85.
    Gustavson, K. H. The Chemistry and Reactivity of Collagen. New York: Academic Press, 1956.Google Scholar
  86. 86.
    Halliday, N. L., and J. J. Tomasek. Mechanical properties of the extracellular matrix influence fibronectin fibril assembly in vitro. Exp. Cell Res. 217:109–117, 1995.CrossRefGoogle Scholar
  87. 87.
    Harris, A. K., D. Stopak, and P. Wild. Fibroblast traction as a mechanism for collagen morphogenesis. Nature 290:249–251, 1981.CrossRefGoogle Scholar
  88. 88.
    Harris, A. K., P. Wild, and D. Stopak. Silicone rubber substrata: A new wrinkle in the study of cell locomotion. Science 208:177–179, 1980.Google Scholar
  89. 89.
    Head, D. A., A. J. Levine, and F. C. MacKintosh. Deformation of cross-linked semiflexible polymer networks. Phys. Rev. Lett. 91:108102, 2003.Google Scholar
  90. 90.
    Heidemann, S. R., and D. Wirtz. Towards a regional approach to cell mechanics. Trends Cell Biol. 14:160–166, 2004.CrossRefGoogle Scholar
  91. 91.
    Helfand, B. T., L. Chang, and R. D. Goldman. The dynamic and motile properties of intermediate filaments. Annu. Rev. Cell Dev. Biol. 19:445–467, 2003.CrossRefGoogle Scholar
  92. 92.
    Helm, C. E., M. E. Fleury, A. H. Zisch, K. C. Boardman, F. Boschetti, and M. A. Swartz. 3D fluid flow directs capillary morphogenesis via biased amplification of VEGF gradients. Proc. Natl. Acd. Sci. USA. 2005 (in press).Google Scholar
  93. 93.
    Helmke, B. P., R. D. Goldman, and P. F. Davies. Rapid displacement of vimentin intermediate filaments in living endothelial cells exposed to flow. Circ. Res. 86:745–752, 2000.Google Scholar
  94. 94.
    Helmke, B. P., A. B. Rosen, and P. F. Davies. Mapping mechanical strain of an endogenous cytoskeletal network in living endothelial cells. Biophys. J. 84:2691–2699, 2003.Google Scholar
  95. 95.
    Hinz, B., G. Celetta, J. J. Tomasek, G. Gabbiani, and C. Chaponnier. Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol. Biol. Cell. 12:2730–2741, 2001.Google Scholar
  96. 96.
    Hinz, B., and G. Gabbiani. Mechanisms of force generation and transmission by myofibroblasts. Curr. Opin. Biotechnol. 14:538–546, 2003.CrossRefGoogle Scholar
  97. 97.
    Hiraoka, N., E. Allen, I. J. Apel, M. R. Gyetko, and S. J. Weiss. Matrix metalloproteinases regulate neovascularization by acting as pericellular fibrinolysins. Cell 95:365–377, 1998.CrossRefGoogle Scholar
  98. 98.
    Huang, H., R. D. Kamm, and R. T. Lee. Cell mechanics and mechanotransduction: Pathways, probes, and physiology. Am. J. Physiol. Cell Physiol. 287:C1–C11, 2004.CrossRefGoogle Scholar
  99. 99.
    Ingber, D. E. Tensegrity: I. Cell structure and hierarchical systems biology. J. Cell Sci. 116:1157–1173, 2003.Google Scholar
  100. 100.
    Ingber, D. E. Tensegrity: II. How structural networks influence cellular information processing networks. J. Cell Sci. 116:1397–1408, 2003.Google Scholar
  101. 101.
    Ingber, D. E. Mechanobiology and diseases of mechanotransduction. Ann. Med. 35:564–577, 2003.Google Scholar
  102. 102.
    Inoué, S. Foundations of confocal scanned imaging in light microscopy. In: Handbook of Biological Confocal Microscopy, edited by J. B. Pawley, 2nd ed., Vol. 1. New York: Plenum Press, 1995, pp. 1–17.Google Scholar
  103. 103.
    Jain, R. K. Transport of molecules in the tumor interstitium: A review. Cancer Res. 47:3039–3051, 1987.Google Scholar
  104. 104.
    Jain, R. K. Transport of molecules, particles, and cells in solid tumors. Ann. Rev. Biomed. Eng. 1:241–263, 1999.CrossRefGoogle Scholar
  105. 105.
    Juvinall, R. C., and K. M. Marshek. Fundamentals of Machine Component Design, 2nd ed. New York: Wiley, 1991.Google Scholar
  106. 106.
    Kahn, L. P., R. J. Carroll, and L. P. Witnauer. Some effects of electrolytes on collagen in solution. Biochim. Biophys. Acta 63:243–254, 1962.CrossRefGoogle Scholar
  107. 107.
    Kamm, R. D. Airway wall mechanics. Ann. Rev. Biomed. Eng. 1:47–72, 1999.CrossRefGoogle Scholar
  108. 108.
    Katz, B.-Z., E. Zamir, A. Bershadsky, Z. Kam, K. M. Yamada, and B. Geiger. Physical state of the extracellular matrix regulates the structure and molecular composition of cell–matrix adhesions. Mol. Biol. Cell. 11:1047–1060, 2000.Google Scholar
  109. 109.
    Keller, H. E. Objective lenses for confocal microscopy. In: Handbook of Biological Confocal Microscopy, edited by J. B. Pawley. New York: Plenum Press, 1995, pp. 111–126.Google Scholar
  110. 110.
    Kerin, A., P. Patwari, K. Kuettner, A. Cole, and A. Grodzinsky. Molecular basis of osteoarthritis: Biomechanical aspects. Cell. Mol. Life Sci. 59:27–35, 2002.Google Scholar
  111. 111.
    Kim, M., N. R. Harris, D. H. Korzick, and J. M. Tarbell. Control of the arteriolar myogenic response by transvascular fluid filtration. Microvasc. Res. 68:30–37, 2004.CrossRefGoogle Scholar
  112. 112.
    Kjæ r, M. Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol. Rev. 84:649–698, 2004.Google Scholar
  113. 113.
    Kleinfeld, D., K. H. Kahler, and P. E. Hockberger. Controlled outgrowth of dissociated neurons on patterned substrates. J. Neurosci. 8:4098–4120, 1988.Google Scholar
  114. 114.
    Knapp, D. M., V. H. Barocas, A. G. Moon, K. Yoo, L. R. Petzold, and R. T. Tranquillo. Rheology of reconstituted type I collagen gel in confined compression. J. Rheol. 41:971–993, 1997.CrossRefGoogle Scholar
  115. 115.
    Knapp, D. M., T. T. Tower, R. T. Tranquillo, and V. H. Barocas. Estimation of cell traction and migration in an isometric cell traction assay. AIChE J. 45:2628–2640, 1999.CrossRefGoogle Scholar
  116. 116.
    Knothe Tate, M. L. Whither flows the fluid in bone? An osteocyte's perspective. J. Biomech. 36:1409–1424, 2003.CrossRefGoogle Scholar
  117. 117.
    Knox, P., S. Crooks, M. C. Scaife, and S. Patel. Role of plasminogen, plasmin, and plasminogen activators in the migration of fibroblasts into plasma clots. J. Cell. Physiol. 132:501–508, 1987.CrossRefGoogle Scholar
  118. 118.
    Kuntz, R. M., and W. M. Saltzman. Neutrophil motility in extracellular matrix gels: Mesh size and adhesion affect speed of migration. Biophys. J. 72:1472–1480, 1997.Google Scholar
  119. 119.
    Lazarides, E. Actin, α-actinin, and tropomyosin interaction in the structural organization of actin filaments in nonmuscle cells. J. Cell Biol. 68:202–219, 1976.CrossRefGoogle Scholar
  120. 120.
    Lazarides, E., and K. Weber. Actin antibody: The specific visualization of actin filaments in non-muscle cells. Proc. Natl. Acad. Sci. U.S.A. 71:2268–2272, 1974.Google Scholar
  121. 121.
    Lee, P. H. A., J. M. Trowbridge, K. R. Taylor, V. B. Morhenn, and R. L. Gallo. Dermatan sulfate proteoglycan and glycosaminoglycan synthesis is induced in fibroblasts by transfer to a three-dimensional extracellular environment. J. Biol. Chem. 279:48640–48646, 2004.Google Scholar
  122. 122.
    Leung, D. Y. M., S. Glagov, and M. B. Mathews. Cyclic stretching stimulates synthesis of matrix components by arterial smooth muscle cells in vitro. Science 191:475–477, 1976.Google Scholar
  123. 123.
    Levick, J. R. Flow through interstitium and other fibrous matrices. Q. J. Exp. Physiol. 72:409–437, 1987.Google Scholar
  124. 124.
    Li, S., J.-L. Guan, and S. Chien. Biochemistry and biomechanics of cell motility. Ann. Rev. Biomed. Eng. 7:9.1–9.46, 2005.Google Scholar
  125. 125.
    Liu, S., D. A. Calderwood, and M. H. Ginsberg. Integrin cytoplasmic domain-binding proteins. J. Cell Sci. 113:3563–3571, 2000.Google Scholar
  126. 126.
    Longas, M. O., and R. Fleischmajer. Immunoelectron microscopy of proteodermatan sulfate in human mid-dermis. Connect. Tissue Res. 13:117–125, 1984.Google Scholar
  127. 127.
    Lorenz, M., V. DesMarais, F. Macaluso, R. H. Singer, and J. Condeelis. Measurement of barbed ends, actin polyerization, and motility in live carcinoma cells after growth factor stimulation. Cell Motil. Cytoskeleton 57:207–217, 2004.CrossRefGoogle Scholar
  128. 128.
    Lyon, M., G. Rushton, and J. T. Gallagher. The interaction of the transforming growth factor-βs with heparin/heparin sulfate is isoform-specific. J. Biol. Chem. 272:18000–18006, 1997.CrossRefGoogle Scholar
  129. 129.
    Maaser, K., K. Wolf, C. E. Klein, et al. Functional hierarchy of simultaneously expressed adhesion receptions: Integrn α2β1 but not CD44 mediates MV3 melanoma cell migration and matrix reorganization within three-dimensional hyaluronan-containing matrices. Mol. Biol. Cell 10:3067–3079, 1999.Google Scholar
  130. 130.
    Maciver, S. K. Microfilament organization and actin-binding proteins. In: The Cytoskelton: Structure and Assembly, edited by J. E. Hesketh and I. F. Pryme, Vol. 1. Greenwich: JAI Press, 1995, pp. 1–45.Google Scholar
  131. 131.
    Majno, G., G. Gabbiani, B. J. Hirschel, G. B. Ryan, and P. R. Statkov. Contraction of granulation tissue in vitro: Similarity to smooth muscle. Science 173:548–550, 1971.Google Scholar
  132. 132.
    Meshel, A. S., Q. Wei, R. S. Adelstein, and M. P. Sheetz. Basic mechanism of three-dimensional collagen fibre transport by fibroblasts. Nat. Cell Biol. 7:157–164, 2005.CrossRefGoogle Scholar
  133. 133.
    Mijailovich, S. M., D. Stamenovic, and J. J. Fredberg. Toward a kinetic theory of connective tissue micromechanics. J. Appl. Physiol. 74:665–681, 1993.Google Scholar
  134. 134.
    Minsky, M. Memoir on inventing the confocal scanning microscope. Scanning 10:128–138, 1988.Google Scholar
  135. 135.
    Mizutani, T., H. Haga, and K. Kawabata. Cellular stiffness response to external deformation: Tensional homeostasis in a single fibroblast. Cell Motil. Cytoskeleton 59:242–248, 2004.CrossRefGoogle Scholar
  136. 136.
    Mochitate, K., P. Pawelek, and F. Grinnell. Stress relaxation of contracted collagen gels: Disruption of actin filament bundles, release of cell surface fibronectin, and down-regulation of DNA and protein synthesis. Exp. Cell Res. 193:198–207, 1991.CrossRefGoogle Scholar
  137. 137.
    Montesano, R., and L. Orci. Tumor-promoting phorbol esters induce angiogenesis in vitro. Cell 42:469–477, 1985.CrossRefGoogle Scholar
  138. 138.
    Mosesson, M. W., K. R. Siebenlist, and D. A. Meh. The structure and biological features of fibrinogen and fibrin. Ann. N. Y. Acad. Sci. 936:11–30, 2001.Google Scholar
  139. 139.
    Mrksich, M., C. S. Chen, Y. Xia, L. E. Dike, D. E. Ingber, and G. M. Whitesides. Controlling cell attachment on contoured surfaces with self-assembled monolates of alkanethiolates on gold. Proc. Natl. Acad. Sci. U.S.A. 93:10775–10778, 1996.CrossRefGoogle Scholar
  140. 140.
    Müller, M. F., and J. D. Ferry. Stress-relaxation in fine fibrin films—Comparison of films prepared with thrombin and ancrod. Biopolymers 23:2311–2323, 1984.Google Scholar
  141. 141.
    Müsch, A. Microtubule organization and function in epithelial cells. Traffic 5:1–9, 2004.Google Scholar
  142. 142.
    Nédélec, F., T. Surrey, and E. Karsenti. Self-organisation and forces in the microtubule cytoskeleton. Curr. Opin. Cell Biol. 15:118–124, 2003.Google Scholar
  143. 143.
    Ng, C. P., C.-L. E. Helm, and M. A. Swartz. Interstitial flow differentially stimulates blood and lymphatic endothelial cell morphogenesis in vitro. Microvasc. Res. 68:258–264, 2004.Google Scholar
  144. 144.
    Ng, C. P., B. Hinz, and M. A. Swartz. Interstitial flow movement is sufficient to induce a fibrotic response in fibroblasts in vitro. J. Cell Sci. 118:4731–4739, 2005.CrossRefGoogle Scholar
  145. 145.
    Ng, C. P., and M. A. Swartz. Fibroblast alignment under interstitial fluid flow using a novel 3D-tissue culture model. Am. J. Physiol. Heart Circ. Physiol. 284:H1771–H1777, 2003.Google Scholar
  146. 146.
    Nusgens, B., C. Merrill, C. Lapiere, and E. Bell. Collagen biosynthesis by cells in a tissue equivalent matrix in vitro. Coll. Relat. Res. 4:351–364, 1984.Google Scholar
  147. 147.
    O'Brien, L. E., K. Tang, E. S. Kats, A. Schutz-Geschwender, J. H. Lipschutz, and K. E. Mostov. ERK and MMPs sequentially regulate distinct stages of epithelial tubule development. Dev. Cell 7:21–32, 2004.CrossRefGoogle Scholar
  148. 148.
    Özerdem, B., and A. Tözeren. Physical response of collagen gels to tensile strain. J. Biomech. Eng. 117:397–401, 1995.Google Scholar
  149. 149.
    Pagan, R., I. Martin, A. Alonso, M. Llobera, and S. Vilaro. Vimentin filaments follow the preexisting cytokeratin network during epithelial–mesenchymal transition of cultured neonatal rat hepatocytes. J. Cell Sci. 222:333–344, 1996.Google Scholar
  150. 150.
    Pankov, R., and K. M. Yamada. Fibronectin at a glance. J. Cell Sci. 115:3861–3863, 2002.CrossRefGoogle Scholar
  151. 151.
    Pantaloni, D., C. Le Clainche, and M.-F. Carlier. Mechanism of actin-based motility. Science 292:1502–1506, 2001.CrossRefGoogle Scholar
  152. 152.
    Pedoe, D. Geometry, A Comprehensive Course. New York: Dover Publications, 1988.Google Scholar
  153. 153.
    Pierce, J. A., and J. B. Hocott. Studies on the collagen and elastin content of the human lung. J. Clin. Invest. 39:8–14, 1960.CrossRefGoogle Scholar
  154. 154.
    Pinney, E., K. Liu, B. Sheeman, and J. Mansbridge. Human three-dimensional fibroblast cultures express angiogenic activity. J. Cell. Physiol. 183:74–82, 2000.CrossRefGoogle Scholar
  155. 155.
    Portet, S., O. Arino, J. Vassy, and D. Schoevaert. Organization of the cytokeratin network in an epithelial cell. J. Theor. Biol. 223:313–333, 2003.CrossRefMathSciNetGoogle Scholar
  156. 156.
    Quinn, T. M., A. J. Grodzinsky, M. D. Buschmann, Y. J. Kim, and E. B. Hunziker. Mechanical compression alters proteoglycan deposition and matrix deformation around individual cells in cartilage explants. J. Cell Sci. 111:573–583, 1998.Google Scholar
  157. 157.
    Ralphs, J. R., A. D. Waggett, and M. Benjamin. Actin stress fibres and cell–cell adhesion molecules in tendons: Organisation in vivo and response to mechanical loading of tendon cells in vitro. Matrix Biol. 21:67–74, 2002.CrossRefGoogle Scholar
  158. 158.
    Ramanujan, S., A. Pluen, T. D. McKee, E. B. Brown, Y. Boucher, and R. K. Jain. Diffusion and convection in collagen gels: Implications for transport in the tumor interstitium. Biophys. J. 83:1650–1660, 2002.Google Scholar
  159. 159.
    Rigaut, J. P. Image cytometry. In: Image Analysis: Methods and Applications, edited by D. P. Häder, 2nd ed. Boca Raton, FL: CRC Press, 2001, pp. 185–207.Google Scholar
  160. 160.
    Roeder, B. A., K. Kokini, J. E. Sturgis, J. P. Robinson, and S. L. Voytik-Harbin. Tensile mechanical properties of three-dimensional type I collagen extracellular matrices with varied microstructure. J. Biomech. Eng. 124:214–222, 2002.Google Scholar
  161. 161.
    Rojkind, M., and M. Mourelle. The liver as a bioecological system: Modifications during regeneration and repair. In: Collagen: Vol. 2: Biochemistry and Biomechanics, edited by M. E. Nimni. Boca Raton, FL: CRC Press, 1988, pp. 137–159.Google Scholar
  162. 162.
    Ronfard, V., and Y. Barrandon. Migration of keratinocytes through tunnels of digested fibrin. Proc. Natl. Acad. Sci. U.S.A. 98:4504–4509, 2001.CrossRefGoogle Scholar
  163. 163.
    Rosenblatt, J., B. Devereux, and D. G. Wallace. Injectable collagen as a pH-sensitive hydrogel. Biomaterials 15:985–995, 1994.CrossRefGoogle Scholar
  164. 164.
    Rosenbloom, J., and W. R. Abrams. Elastin and the microfibrillar apparatus. In: Connective Tissue and Its Heritable Disorders: Molecular, Genetic and Medical Aspects, edited by P. M. Royce and B. Steinmann, 2nd ed. New York: Wiley-Liss, 2002, pp. 249–269.Google Scholar
  165. 165.
    Roska, F. J., and J. D. Ferry. Studies of fibrin film: 1. Stress-relaxation and birefringence. Biopolymers 21:1811–1832, 1982.Google Scholar
  166. 166.
    Rowley, J. A., G. Madlambayan, and D. J. Mooney. Alginate hydrogels as synthetic extracellular matrix materials. Biomaterials 20:45–53, 1999.CrossRefGoogle Scholar
  167. 167.
    Ryan, E. A., L. F. Mockros, J. W. Weisel, and L. Lorand. Structural origins of fibrin clot rheology. Biophys. J. 77:2813–2826, 1999.Google Scholar
  168. 168.
    Sakiyama-Elbert, S. E., and J. A. Hubbell. Development of fibrin derivatives for controlled release of heparin-binding growth factors. J. Control. Release 65:389–402, 2000.CrossRefGoogle Scholar
  169. 169.
    Saltzman, W. M., M. L. Radomsky, K. J. Whaley, and R. A. Cone. Antibody diffusion in human cervical mucus. Biophys. J. 66:508–515, 1994.Google Scholar
  170. 170.
    Sawada, Y., and M. P. Sheetz. Force transduction by Triton cytoskeletons. J. Cell Biol. 156:609–615, 2002.CrossRefGoogle Scholar
  171. 171.
    Sawhney, R. K., and J. Howard. Slow local movements of collagen fibers by fibroblasts drive the rapid global self-organization of collagen gels. J. Cell Biol. 157:1083–1091, 2002.CrossRefGoogle Scholar
  172. 172.
    Schmidt, C. E., A. F. Horwitz, D. A. Lauffenburger, and M. P. Sheetz. Integrin–cytoskeletal interactions in migrating fibroblasts are dynamic, asymmetric, and regulated. J. Cell Biol. 123:977–991, 1993.CrossRefGoogle Scholar
  173. 173.
    Schönherr, E., and H.-J. Hausser. Extracellular matrix and cytokines: A functional unit. Dev. Immunol. 7:89–101, 2000.Google Scholar
  174. 174.
    Schor, S. L., T. D. Allen, and C. J. Harrison. Cell migration through three-dimensional gels of native collagen fibres: Collagenolytic activity is not required for the migration of two permanent cell lines. J. Cell Sci. 46:171–186, 1980.Google Scholar
  175. 175.
    Schwartz, M. A. Integrin signaling revisited. Trends Cell Biol. 11:466–470, 2001.CrossRefGoogle Scholar
  176. 176.
    Scott, J. E. Extracellular matrix, supramolecular organisation and shape. J. Anat. 187:259–269, 1995.Google Scholar
  177. 177.
    Serini, G., M.-L. Bochaton-Piallat, P. Ropraz, et al. The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-β1. J. Cell Biol. 142:873–881, 1998.Google Scholar
  178. 178.
    Shoeman, R. L., and P. Traub. Intermediate filament proteins. In: The Cytoskeleton: Structure and Assembly, edited by J. E. Hekseth and I. F. Pryme, Vol. 1. Greenwich: JAI Press, 1995, pp. 205–255.Google Scholar
  179. 179.
    Shreiber, D. I., V. H. Barocas, and R. T. Tranquillo. Temporal variations in cell migration and traction during fibroblast-mediated gel compaction. Biophys. J. 84:4102–4114, 2003.Google Scholar
  180. 180.
    Silver, F. H., L. M. Siperko, and G. P. Seehra. Mechanobiology of force transduction in dermal tissue. Skin Res. Technol. 9:3–23, 2003.CrossRefGoogle Scholar
  181. 181.
    Simpson-Haidaris, P. J., and B. Rybarczyk. Tumors and fibrinogen: The role of fibrinogen as an extracellular matrix protein. Ann. N. Y. Acad. Sci. 936:406–425, 2001.Google Scholar
  182. 182.
    Skalli, O., P. Ropraz, A. Trzeciak, G. Benzonana, D. Gillessen, and G. Gabbiani. A monoclonal antibody against a-smooth muscle actin: A new probe for smooth muscle differentiation. J. Cell Biol. 103:2787–2796, 1986.CrossRefGoogle Scholar
  183. 183.
    Spronk, H. M. H., J. W. P. Govers-Riemslag, and H. Ten Cate. The blood coagulation system as a molecular machine. Bioessays 25:1220–1228, 2003.CrossRefGoogle Scholar
  184. 184.
    Stephens, D. J., and V. J. Allan. Light microscopy techniques for live cell imaging. Science 300:82–86, 2003.CrossRefGoogle Scholar
  185. 185.
    Swartz, M. A. The physiology of the lymphatic system. Adv. Drug Delivery Rev. 50:3–20, 2001.CrossRefGoogle Scholar
  186. 186.
    Swartz, M. A. Signaling in morphogenesis: Transport cues in morphogenesis. Curr. Opin. Biotechnol. 14:547–550, 2003.CrossRefGoogle Scholar
  187. 187.
    Tada, S., and J. M. Tarbell. Interstitial flow through the internal elastic lamina affects shear stress on arterial smooth muscle cells. Am. J. Physiol. Heart Circ. Physiol. 278:H1589–H1597, 2000.Google Scholar
  188. 188.
    Tada, S., and J. M. Tarbell. Internal elastic lamina affects the distribution of macromolecules in the arterial wall: A computational study. Am. J. Physiol. Heart Circ. Physiol. 287:H905–H913, 2004.CrossRefGoogle Scholar
  189. 189.
    Takahashi, A., R. Kita, T. Shinozaki, K. Kubota, and M. Kaibara. Real-space observation of three-dimensional network structure of hydrated fibrin gel. Colloid Polym. Sci. 281:832–838, 2003.CrossRefGoogle Scholar
  190. 190.
    Tamariz, E., and F. Grinnell. Modulation of fibroblast morphology and adhesion during collagen matrix remodeling. Mol. Biol. Cell. 13:3915–3929, 2002.CrossRefGoogle Scholar
  191. 191.
    Tan, J. L., J. Tien, D. M. Pirone, D. S. Gray, K. Bhadriraju, and C. S. Chen. Cells lying on a bed of microneedles: An approach to isolate mechanical force. Proc. Natl. Acad. Sci. U.S.A. 100:1484–1489, 2003.Google Scholar
  192. 192.
    Tarbell, J. M. Mass transport in arteries and the localization of atherosclerosis. Ann. Rev. Biomed. Eng. 5:79–118, 2003.CrossRefGoogle Scholar
  193. 193.
    Thi, M. M., J. M. Tarbell, S. Weinbaum, and D. C. Spray. The role of the glycocalyx in reorganization of the actin cytoskeleton uner fluid shear stress: A “bumper-car” model. Proc. Natl. Acad. Sci. U.S.A. 101:16483–16488, 2004.CrossRefGoogle Scholar
  194. 194.
    Tomasek, J. J., G. Gabbiani, B. Hinz, C. Chaponnier, and R. A. Brown. Myofibroblasts and mechanoregulation of connective tissue remodeling. Nat. Rev. Mol. Cell Biol. 3:349–363, 2002.CrossRefGoogle Scholar
  195. 195.
    Toyoizumi, R., K. Mogi, and S. Takeuchi. Individual epiblast cells acquired invasiveness precedent to the primitive streak formation in the chick embryo. Zool. Sci. 14:313–320, 1997.Google Scholar
  196. 196.
    Trächslin, J., M. Koch, and M. Chiquet. Rapid and reversible regulation of collagen XII expression by changes in tensile stress. Exp. Cell Res. 247:320–328, 1999.Google Scholar
  197. 197.
    Tranquillo, R. T. Self-organization of tissue-equivalents: The nature and role of contact guidance. Biochem. Soc. Symp. 65:27–42, 1997.Google Scholar
  198. 198.
    Tseng, Y., T. P. Kole, and D. Wirtz. Micromechanical mapping of live cells by multiple-particle-tracking microrheology. Biophys. J. 83:3162–3176, 2002.CrossRefGoogle Scholar
  199. 199.
    Tseng, Y. and D. Wirtz. Mechanics and multiple-particle tracking microheterogeneity of α-actinin cross-linked actin filament networks. Biophys. J. 81: 1643–1656, 2001.Google Scholar
  200. 200.
    Tuan, T. L., A. Song, S. Chang, S. Younai, and M. E. Nimni. In vitro fibroplasia: Matrix contraction, cell growth, and collagen production of fibroblasts cultured in fibrin gels. Exp. Cell Res. 223:127–134, 1996.CrossRefGoogle Scholar
  201. 201.
    von der Mark, K., and L. Sorokin. Adhesive glycoproteins. In: Connective Tissue and Its Heritable Disorders: Molecular, Genetic and Medical Aspects, edited by P. M. Royce and B. Steinmann, 2nd ed. New York: Wiley-Liss, 2002, pp. 293–328.Google Scholar
  202. 202.
    Vanni, S., B. C. Lagerholm, C. Otey, D. L. Taylor, and F. Lanni. Internet-based image analysis quantifies contractile behavior of individual fibroblasts inside model tissue. Biophys. J. 84:2715–2727, 2003.Google Scholar
  203. 203.
    Viidik, A. Tendons and ligaments. In: Extracellular Matrix, Vol. 1: Tissue Function, edited by W. D. Comper, Vol. 1. Amsterdam: Harwood Academic Publishers GmbH, 1996, pp. 303–327.Google Scholar
  204. 204.
    Visser, T., J. Oud, and G. Brakenhoff. Refractive index and axial distance measurements in 3-D microscopy. Optik 90:17–19, 1992.Google Scholar
  205. 205.
    Voytik-Harbin, S. L., A. O. Brightman, B. Z. Waisner, J. P. Robinson, and C. H. Lamar. Small intestinal submucosa: A tissue-derived extracellular matrix that promotes tissue-specific growth and differentiation of cells in vitro. Tissue Eng. 4:157–174, 1998.Google Scholar
  206. 206.
    Voytik-Harbin, S. L., B. A. Roeder, J. E. Sturgis, K. Kokini, and J. P. Robinson. Simultaneous mechanical loading and confocal reflection microscopy for three-dimensional microbiomechanical analysis of biomaterials and tissue constructs. Microsc. Microanal. 9:74–85, 2003.CrossRefGoogle Scholar
  207. 207.
    Wang, Y.-L. Reorganization of actin filament bundles in living fibroblasts. J. Cell Biol. 99:1478–1485, 1984.Google Scholar
  208. 208.
    Wang, N., J. P. Butler, and D. E. Ingber. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127, 1993.Google Scholar
  209. 209.
    Wang, H.-B., M. Dembo, S. K. Hanks, and Y.-L. Wang. Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl. Acad. Sci. U.S.A. 98:11295–11300, 2001.Google Scholar
  210. 210.
    Wang, N., and D. E. Ingber. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys. J. 66:2181–2189, 1994.CrossRefGoogle Scholar
  211. 211.
    Wang, N., E. Ostuni, G. M. Whitesides, and D. E. Ingber. Micropatterning tractional forces in living cells. Cell Motil. Cytoskeleton 52:97–106, 2002.CrossRefGoogle Scholar
  212. 212.
    Wang, S., and J. M. Tarbell. Effect of fluid flow on smooth muscle cells in a 3-dimensional collagen gel model. Arterioscler. Thromb. Vasc. Biol. 20:2220–2225, 2000.Google Scholar
  213. 213.
    Waterman-Storer, C., D. Y. Duey, K. L. Weber, et al. Microtubules remodel actomyosin networks in Xenopus egg extracts via two mechanisms of f-actin transport. J. Cell Biol. 150:361–376, 2000.Google Scholar
  214. 214.
    Weber, K., E. Lazarides, R. D. Goldman, A. Vogel, and R. Pollack. Localization and distribution of actin fibers in normal, transformed and revertant cells. Cold Spring Harb. Symp. Quant. Biol. 39:363–369, 1974.Google Scholar
  215. 215.
    Weinbaum, S., X. Zhang, Y. Han, H. Vink, and S. C. Cowin. Mechanotransduction and flow across the endothelial glycocalyx. Proc. Natl. Acad. Sci. U.S.A. 100:7988–7995, 2003.CrossRefGoogle Scholar
  216. 216.
    Williams, B. R., R. A. Gelman, D. C. Poppke, and K. A. Piez. Collagen fibril formation. J. Biol. Chem. 253:6578–6585, 1978.Google Scholar
  217. 217.
    Winter, H. H., and M. Mours. Rheology of polymers near liquid–solid transitions. Adv. Polym. Sci. 134:165–234, 1997.Google Scholar
  218. 218.
    Wolf, K., I. Mazo, H. Leung, et al. Compensation mechanism in tumor cell migration: Mesenchymal-amoeboid transition after blocking pericellular proteolysis. J. Cell Biol. 160:267–277, 2003.CrossRefGoogle Scholar
  219. 219.
    Wong, J. Y., A. Velasco, P. Rajagopalan, and Q. Pham. Directed movement of vascular smooth muscle cells on gradient-compliant hydrogels. Langmuir 19:1908–1913, 2003.Google Scholar
  220. 220.
    Wood, G. C., and M. K. Keech. Formation of fibrils from collagen solutions: 1. Effect of experimental conditions—kinetic and electron-microscope studies. Biochem. J. 75:588–598, 1960.Google Scholar
  221. 221.
    Xu, J., Y. Tseng, and D. Wirtz. Strain-hardening of actin filament networks- regulation by the dynamic cross-linking prottein α-actinin. J. Biol. Chem. 275:35886–35892, 2000.Google Scholar
  222. 222.
    Yang, S., J. Graham, J. W. Kahn, E. A. Schwartz, and M. E. Gerritsen. Functional roles for PECAM-1 (CD31) and VE-Cadherin (CD144) in tube assembly and lumen formation in three-dimensional collagen gels. Am. J. Pathol. 155:887–895, 1999.Google Scholar
  223. 223.
    Yeung, T., P. C. Georges, L. A. Flanagan, et al. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil. Cytoskeleton 60:24–34, 2005.Google Scholar
  224. 224.
    Zimerman, B., T. Volberg, and B. Geiger. Early molecular events in the assembly of the focal adhesion-stress fiber complex during fibroblast spreading. Cell Motil. Cytoskeleton 58:143–159, 2004.CrossRefGoogle Scholar

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© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Biomedical Engineering DepartmentNorthwestern UniversityEvanston
  2. 2.Integrative Biosciences InstituteÉcole Polytechnique Fédérale de Lausanne (EPFL)LausanneSwitzerland
  3. 3.Laboratory for Mechanobiology and MorphogenesisIntegrative Biosciences Institute, Swiss Federal Institute of Technology Lausanne (EPFL)LausanneSwitzerland

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