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Nanotechnology for Cell–Substrate Interactions

  • Nanobioengineering
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Abstract

In the pursuit to understand the interaction between cells and their underlying substrates, the life sciences are beginning to incorporate micro- and nanotechnology-based tools to probe and measure cells. The development of these tools portends endless possibilities for new insights into the fundamental relationships between cells and their surrounding microenvironment that underlie the physiology of human tissue. Here, we review techniques and tools that have been used to study how a cell responds to the physical factors in its environment. We also discuss unanswered questions that could be addressed by these approaches to better elucidate the molecular processes and mechanical forces that dominate the interactions between cells and their physical scaffolds.

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REFERENCES

  1. Abercrombie, M., J. E. Heaysman, and S. M. Pegrum. The locomotion of fibroblasts in culture. IV. Electron microscopy of the leading lamella. Exp. Cell Res. 67:359–367, 1971.

    Article  PubMed  CAS  Google Scholar 

  2. Abrams, G. A., S. L. Goodman, P. F. Nealey, M. Franco, and C. J. Murphy. Nanoscale topography of the basement membrane underlying the corneal epithelium of the rhesus macaque. Cell Tissue Res. 299:39–46, 2000.

    PubMed  CAS  Google Scholar 

  3. Abrams, G. A., C. J. Murphy, Z. Y. Wang, P. F. Nealey, and D. E. Bjorling. Ultrastructural basement membrane topography of the bladder epithelium. Urol. Res. 31:341–346, 2003.

    Article  PubMed  Google Scholar 

  4. Alberts, B., A. Johnson, J. Lewis, M. Raff, K. Roberts, and P. Walter. Molecular Biology of the Cell. New York, NY: Garland Science, 2002, 1616 pp.

    Google Scholar 

  5. Alenghat, F. J., B. Fabry, K. Y. Tsai, W. H. Goldmann, and D. E. Ingber. Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer. Biochem. Biophys. Res. Commun. 277:93–99, 2000.

    Article  PubMed  CAS  Google Scholar 

  6. Alenghat, F. J., and D. E. Ingber. Mechanotransduction: all signals point to cytoskeleton, matrix, and integrins. Sci. STKE, 2002:PE6, 2002.

    Google Scholar 

  7. Ashkin, A., and J. M. Dziedzic. Optical trapping and manipulation of viruses and bacteria. Science 235:1517–1520, 1987.

    PubMed  CAS  Google Scholar 

  8. Bain, C. D., J. Evall, and G. M. Whitesides. Formation of monolayers by the coadsorption of thiols on gold: Variation in the head group, tail group, and solvent. J. Am. Chem. Soc. 111:7155–7164, 1989.

    Article  CAS  Google Scholar 

  9. Bain, C. D., and G. M. Whitesides. Correlations between wettability and structure in monolayers of alkanethiols adsorbed on gold. J. Am. Chem. Soc. 110:3665–3666, 1988.

    Article  CAS  Google Scholar 

  10. Bain, C. D., and G. M. Whitesides. Formation of monolayers by the coadsoption of thiols on gold: Variation in the length of the alkyl chain. J. Am. Chem. Soc. 111:7164–7175, 1989.

    Article  CAS  Google Scholar 

  11. 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. Nat. Cell Biol. 3:466–472, 2001.

    Article  PubMed  CAS  Google Scholar 

  12. Balss, K. M., B. D. Coleman, C. H. Lansford, R. T. Haasch, and P. W. Bohn. Active spatiotemporal control of electrochemical reactions by coupling to in-plane potential gradients. J. Phys. Chem. 105:8970–8978, 2001.

    CAS  Google Scholar 

  13. Beningo, K. A., M. Dembo, I. Kaverina, J. V. Small, and Y. L. Wang. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J. Cell Biol. 153:881–888, 2001.

    Article  PubMed  CAS  Google Scholar 

  14. Beningo, K. A., M. Dembo, and Y. L. Wang. Responses of fibroblasts to anchorage of dorsal extracellular matrix receptors. Proc. Natl. Acad. Sci. USA 101:18024–18029, 2004.

    Article  PubMed  CAS  Google Scholar 

  15. Bernard, A., E. Delamarche, H. Schmid, B. Michel, H. R. Bosshard, and H. Biebuyck. Printing patterns of proteins. Langmuir 14:2225–2229, 1998.

    Article  CAS  Google Scholar 

  16. Brock, A., E. Chang, C. C. Ho, P. LeDuc, X. Jiang, G. M. Whitesides, and D. E. Ingber. Geometric determinants of directional cell motility revealed using microcontact printing. Langmuir 19:1611–1617, 2003.

    Article  PubMed  CAS  Google Scholar 

  17. Burns, M. M., J. M. Fournier, and J. A. Golovchenko. Optical matter—Crystallization and binding in intense optical-fields. Science 249:749–754, 1990.

    PubMed  Google Scholar 

  18. Burridge, K., and M. Chrzanowska-Wodnicka. Focal adhesions, contractility, and signaling. Annu. Rev. Cell Dev. Biol. 12:463–518, 1996.

    Article  PubMed  CAS  Google Scholar 

  19. Burton, K., J. H. Park, and D. L. Taylor. Keratocytes generate traction forces in two phases. Mol. Biol. Cell 10:3745–3769, 1999.

    PubMed  CAS  Google Scholar 

  20. Burton, K., and D. L. Taylor. Traction forces of cytokinesis measured with optically modified elastic substrata. Nature 385:450–454, 1997.

    Article  PubMed  CAS  Google Scholar 

  21. Carter, S. B. Haptotaxis and the mechanism of cell motility. Nature 213:256–260, 1967.

    PubMed  CAS  Google Scholar 

  22. Charras, G. T., and M. A. Horton. Single cell mechanotransduction and its modulation analyzed by atomic force microscope indentation. Biophys. J. 82:2970–2981, 2002.

    PubMed  CAS  Google Scholar 

  23. Chen, C. S., J. L. Alonso, E. Ostuni, G. M. Whitesides, and D. E. Ingber. Cell shape provides global control of focal adhesion assembly. Biochem. Biophys. Res. Commun. 307:355–361, 2003.

    Article  PubMed  CAS  Google Scholar 

  24. Chen, J., B. Fabry, E. L. Schiffrin, and N. Wang. Twisting integrin receptors increases endothelin-1 gene expression in endothelial cells. Am. J. Physiol. Cell Physiol. 280:C1475–C1484, 2001.

    PubMed  CAS  Google Scholar 

  25. 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.

    Article  PubMed  CAS  Google Scholar 

  26. Chen, C. S., J. Tan, and J. Tien. Mechanotransduction at cell-matrix and cell-cell contacts. Annu. Rev. Biomed. Eng. 6:275–302, 2004.

    Article  PubMed  CAS  Google Scholar 

  27. Chicurel, M. E., R. H. Singer, C. J. Meyer, and D. E. Ingber. Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions. Nature 392:730–733, 1998.

    Article  PubMed  CAS  Google Scholar 

  28. Choquet, D., D. P. Felsenfeld, and M. P. Sheetz. Extracellular matrix rigidity causes strengthening of integrin-cytoskeleton linkages. Cell 88:39–48, 1997.

    Article  PubMed  CAS  Google Scholar 

  29. Chrzanowska-Wodnicka, M., and K. Burridge. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J. Cell Biol. 133:1403–1415, 1996.

    Article  PubMed  CAS  Google Scholar 

  30. Coussen, F., D. Choquet, M. P. Sheetz, and H. P. Erickson. Trimers of the fibronectin cell adhesion domain localize to actin filament bundles and undergo rearward translocation. J. Cell Sci. 115:2581–2590, 2002.

    PubMed  CAS  Google Scholar 

  31. Curtis, A. S. The mechanism of adhesion of cells to glass. A study by interference reflection microscopy. J. Cell Biol. 20:199–215, 1964.

    Article  PubMed  CAS  Google Scholar 

  32. Curtis, A. S., and M. Varde. Control of cell behavior: Topological factors. J. Natl. Cancer Inst. 33:15–26, 1964.

    PubMed  CAS  Google Scholar 

  33. Curtis, A. S., C. D. Wilkinson, J. Crossan, C. Broadley, H. Darmani, K. K. Johal, H. Jorgensen, and W. Monaghan. An in vivo microfabricated scaffold for tendon repair. Eur. Cell Mater. 9:50–57, 2005.

    PubMed  CAS  Google Scholar 

  34. Dalby, M. J., M. O. Riehle, D. S. Sutherland, H. Agheli, and A. S. Curtis. Morphological and microarray analysis of human fibroblasts cultured on nanocolumns produced by colloidal lithography. Eur. Cell Mater. 9:1–8, 2005.

    PubMed  CAS  Google Scholar 

  35. Dalby, M. J., S. J. Yarwood, M. O. Riehle, H. J. Johnstone, S. Affrossman, and A. S. Curtis. Increasing fibroblast response to materials using nanotopography: Morphological and genetic measurements of cell response to 13-nm-high polymer demixed islands. Exp. Cell Res. 276:1–9, 2002.

    Article  PubMed  CAS  Google Scholar 

  36. Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75:519–560, 1995.

    PubMed  CAS  Google Scholar 

  37. Davies, P. F., A. Robotewskyj, and M. L. Griem. Quantitative studies of endothelial cell adhesion. Directional remodeling of focal adhesion sites in response to flow forces. J. Clin. Invest. 93:2031–2038, 1994.

    PubMed  CAS  Google Scholar 

  38. Dembo, M., T. Oliver, A. Ishihara, and K. Jacobson. Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys. J. 70:2008–2022, 1996.

    PubMed  CAS  Google Scholar 

  39. Dembo, M., and Y. L. Wang. Stresses at the cell-to-substrate interface during locomotion of fibroblasts. Biophys. J. 76:2307–2316, 1999.

    PubMed  CAS  Google Scholar 

  40. Dertinger, S. K., D. T. Chiu, N. L. Jeon, and G. M. Whitesides. Generation of gradients having complex shapes using microfluidics networks. Anal. Chem. 73:1240–1246, 2001.

    Article  CAS  Google Scholar 

  41. Dertinger, S. K., X. Jiang, Z. Li, V. N. Murthy, and G. M. Whitesides. Gradients of substrate-bound laminin orient axonal specification of neurons. Proc. Natl. Acad. Sci. USA 99:12542–12547, 2002.

    Article  PubMed  CAS  Google Scholar 

  42. Dike, L. E., C. S. Chen, M. Mrksich, J. Tien, G. M. Whitesides, and D. E. Ingber. Geometric control of switching between growth, apoptosis, and differentiation during angiogenesis using micropatterned substrates. In Vitro Cell Dev. Biol. Anim. 35:441–448, 1999.

    PubMed  CAS  Google Scholar 

  43. Doornaert, B., V. Leblond, E. Planus, S. Galiacy, V. M. Laurent, G. Gras, D. Isabey, and C. Lafuma. Time course of actin cytoskeleton stiffness and matrix adhesion molecules in human bronchial epithelial cell cultures. Exp. Cell Res. 287:199–208, 2003.

    Article  PubMed  CAS  Google Scholar 

  44. du Roure, O., A. Saez, A. Buguin, R. H. Austin, P. Chavrier, P. Siberzan, and B. Ladoux. Force mapping in epithelial cell migration. Proc. Natl. Acad. Sci. USA 102:2390–2395, 2005.

    Article  PubMed  CAS  Google Scholar 

  45. Elias, K. L., R. L. Price, and T. J. Webster. Enhanced functions of osteoblasts on nanometer diameter carbon fibers. Biomaterials 23:3279–3287, 2002.

    Article  PubMed  CAS  Google Scholar 

  46. Fabry, B., G. N. Maksym, J. P. Butler, M. Glogauer, D. Navajas, and J. J. Fredberg. Scaling the microrheology of living cells. Phys. Rev. Lett. 87:148102, 2001.

    Article  PubMed  CAS  Google Scholar 

  47. Feynman, R. P. There's plenty of room at the bottom. American Physical Society. Pasadena, CA: California Institute of Technology, 1959.

    Google Scholar 

  48. Finer, J. T., R. M. Simmons, and J. A. Spudich. Single myosin molecule mechanics: Piconewton forces and nanometre steps. Nature 368:113–119, 1994.

    Article  PubMed  CAS  Google Scholar 

  49. Flemming, R. G., C. J. Murphy, G. A. Abrams, S. L. Goodman, and P. F. Nealey. Effects of synthetic micro- and nano-structured surfaces on cell behavior. Biomaterials 20:573–588, 1999.

    Article  PubMed  CAS  Google Scholar 

  50. Foley, J. D., E. W. Grunwald, P. F. Nealey, and C. J. Murphy. Cooperative modulation of neuritogenesis by PC12 cells by topography and nerve growth factor. Biomaterials 26:3639–3644, 2005.

    Article  PubMed  CAS  Google Scholar 

  51. Folkman, J., and A. Moscona. Role of cell shape in growth control. Nature 273:345–349, 1978.

    Article  PubMed  CAS  Google Scholar 

  52. Galbraith, C. G., and M. P. Sheetz. A micromachined device provides a new bend on fibroblast traction forces. Proc. Natl. Acad. Sci. USA 94:9114–9118, 1997.

    Article  PubMed  CAS  Google Scholar 

  53. Galbraith, C. G., and M. P. Sheetz. Forces on adhesive contacts affect cell function. Curr. Opin. Cell Biol. 10:566–571, 1998.

    Article  PubMed  CAS  Google Scholar 

  54. Galbraith, C. G., and M. P. Sheetz. Keratocytes pull with similar forces on their dorsal and ventral surfaces. J. Cell Biol. 147:1313–1324, 1999.

    Article  PubMed  CAS  Google Scholar 

  55. Galbraith, C. G., K. M. Yamada, and M. P. Sheetz. The relationship between force and focal complex development. J. Cell Biol. 159:695–705, 2002.

    Article  PubMed  CAS  Google Scholar 

  56. Gaudet, C., W. A. Marganski, S. Kim, C. T. Brown, V. Gunderia, M. Dembo, and J. Y. Wong. Influence of type I collagen surface density on fibroblast spreading, motility, and contractility. Biophys. J. 85:3329–3335, 2003.

    PubMed  CAS  Google Scholar 

  57. Geiger, B., A. Bershadsky, R. Pankov, and K. M. Yamada. Transmembrane extracellular matrix–cytoskeleton crosstalk. Nat. Rev. Mol. Cell Biol. 2:793–805, 2001.

    Article  PubMed  CAS  Google Scholar 

  58. Giannone, G., G. Jiang, D. H. Sutton, D. R. Critchley, and M. P. Sheetz. Talin1 is critical for force-dependent reinforcement of initial integrin-cytoskeleton bonds but not tyrosine kinase activation. J. Cell Biol. 163:409–419, 2003.

    Article  PubMed  CAS  Google Scholar 

  59. Ginger, D. S., H. Zhang, and C. A. Mirkin. The evolution of dip-pen nanolithography. Angew Chem. Int. Ed. Engl. 43:30–45, 2004.

    Article  PubMed  CAS  Google Scholar 

  60. Harris, A. Behavior of cultured cells on substrata of variable adhesiveness. Exp. Cell Res. 77:285–297, 1973.

    Article  PubMed  CAS  Google Scholar 

  61. Harris, A. K., Jr. Tissue culture cells on deformable substrata: Biomechanical implications. J. Biomech. Eng. 106:19–24, 1984.

    PubMed  Google Scholar 

  62. 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.

    PubMed  CAS  Google Scholar 

  63. Helfman, D. M., E. T. Levy, C. Berthier, M. Shtutman, D. Riveline, I. Grosheva, A. Lachish-Zalait, M. Elbaum, and A. D. Bershadsky. Caldesmon inhibits nonmuscle cell contractility and interferes with the formation of focal adhesions. Mol. Biol. Cell 10:3097–3112, 1999.

    PubMed  CAS  Google Scholar 

  64. Hu, S., J. Chen, B. Fabry, Y. Numaguchi, A. Gouldstone, D. E. Ingber, J. J. Fredberg, J. P. Butler, and N. Wang. Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. Am. J. Physiol. Cell Physiol. 285:C1082–C1090, 2003.

    PubMed  CAS  Google Scholar 

  65. Hu, S., L. Eberhard, J. Chen, J. C. Love, J. P. Butler, J. J. Fredberg, G. M. Whitesides, and N. Wang. Mechanical anisotropy of adherent cells probed by a three-dimensional magnetic twisting device. Am. J. Physiol. Cell Physiol. 287:C1184–C1191, 2004.

    Article  PubMed  CAS  Google Scholar 

  66. Hua, F., Y. G. Sun, A. Gaur, M. A. Meitl, L. Bilhaut, L. Rotkina, J. F. Wang, P. Geil, M. Shim, J. A. Rogers, and A. Shim. Polymer imprint lithography with molecular-scale resolution. Nano Lett. 4:2467–2471, 2004.

    Article  CAS  Google Scholar 

  67. Huang, S., C. S. Chen, and D. E. Ingber. Control of cyclin D1, p27(Kip1), and cell cycle progression in human capillary endothelial cells by cell shape and cytoskeletal tension. Mol. Biol. Cell 9:3179–3193, 1998.

    PubMed  CAS  Google Scholar 

  68. Ingber, D. E. Mechanobiology and diseases of mechanotransduction. Ann. Med. 35:564–577, 2003.

    Article  PubMed  Google Scholar 

  69. Ingber, D. E. Tensegrity I. Cell structure and hierarchical systems biology. J.Cell Sci. 116:1157–1173, 2003.

    Article  PubMed  CAS  Google Scholar 

  70. Ingber, D. E. Tensegrity II. How structural networks influence cellular information processing networks. J. Cell Sci. 116:1397–1408, 2003.

    Article  PubMed  CAS  Google Scholar 

  71. James, C. D., R. C. Davis, L. Kam, H. G. Craighead, M. Isaacson, J. N. Turner, and W. Shain. Patterned protein layers on solid substrates by thin stamp microcontact printing. Langmuir 14:741–744, 1998.

    Article  CAS  Google Scholar 

  72. Jeon, N. L., H. Baskaran, S. K. Dertinger, G. M. Whitesides, L. Van De Water, and M. Toner. Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat. Biotech. 20:826–830, 2002.

    CAS  Google Scholar 

  73. Jiang, X., D. A. Bruzewicz, A. P. Wong, M. Piel, and G. M. Whitesides. Directing cell migration with asymmetric micropatterns. Proc. Natl. Acad. Sci. USA 102:975–978, 2005.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  75. Jiang, G. Y., G. Giannone, D. R. Critchley, E. Fukumoto, and M. P. Sheetz. Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin. Nature 424:334–337, 2003.

    Article  PubMed  CAS  Google Scholar 

  76. Kong, H. J., T. R. Polte, E. Alsberg, and D. J. Mooney. FRET measurements of cell-traction forces and nano-scale clustering of adhesion ligands varied by substrate stiffness. Proc. Natl. Acad. Sci. USA 102:4300–4305, 2005.

    Article  PubMed  CAS  Google Scholar 

  77. Laurent, V. M., S. Kasas, A. Yersin, T. E. Schaffer, S. Catsicas, G. Dietler, A. B. Verkhovsky, and J. J. Meister. Gradient of rigidity in the lamellipodia of migrating cells revealed by atomic force microscopy. Biophys. J. 89:667–675, 2005.

    Article  PubMed  CAS  Google Scholar 

  78. Lee, G. M., and R. F. Loeser. Cell surface receptors transmit sufficient force to bend collagen fibrils. Exp. Cell Res. 248:294–305, 1999.

    Article  PubMed  CAS  Google Scholar 

  79. Lee, J., M. Leonard, T. Oliver, A. Ishihara, and K. Jacobson. Traction forces generated by locomoting keratocytes. J. Cell Biol. 127:1957–1964, 1994.

    Article  PubMed  CAS  Google Scholar 

  80. Lee, K. B., S. J. Park, C. A. Mirkin, J. C. Smith, and M. Mrksich. Protein nanoarrays generated by dip-pen nanolithography. Science 295:1702–1705, 2002.

    Article  PubMed  CAS  Google Scholar 

  81. Lehnert, D., B. Wehrle-Haller, C. David, U. Weiland, C. Ballestrem, B. A. Imhof, and M. Bastmeyer. Cell behaviour on micropatterned substrata: Limits of extracellular matrix geometry for spreading and adhesion. J. Cell Sci. 117:41–52, 2004.

    Article  PubMed  CAS  Google Scholar 

  82. Leung, D. Y., 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.

    PubMed  CAS  Google Scholar 

  83. Li, F., S. D. Redick, H. P. Erickson, and V. T. Moy. Force measurements of the alpha5beta1 integrin-fibronectin interaction. Biophys. J. 84:1252–1262, 2003.

    PubMed  CAS  Google Scholar 

  84. Liedberg, B., and P. Tengvall. Molecular gradients of omega-substituted alkanethiols on gold: Preparation and characterization. Langmuir 11:3821–3827, 1995.

    Article  CAS  Google Scholar 

  85. Lin, F., C. M. Nguyen, S. J. Wang, W. Saadi, S. P. Gross, and N. L. Jeon. Neutrophil migration in opposing chemoattractant gradients using microfluidic chemotaxis devices. Ann. Biomed. Eng. 33:475–482, 2005.

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  87. Mack, P. J., M. R. Kaazempur-Mofrad, H. Karcher, R. T. Lee, and R. D. Kamm. Force-induced focal adhesion translocation: Effects of force amplitude and frequency. Am. J. Physiol. Cell Physiol. 287:C954–C962, 2004.

    Article  PubMed  CAS  Google Scholar 

  88. Maniotis, A. J., C. S. Chen, and D. E. Ingber. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc. Natl. Acad. Sci. USA 94:849–854, 1997.

    Article  PubMed  CAS  Google Scholar 

  89. Matthews, B. D., D. R. Overby, F. J. Alenghat, J. Karavitis, Y. Numaguchi, P. G. Allen, and D. E. Ingber. Mechanical properties of individual focal adhesions probed with a magnetic microneedle. Biochem. Biophys. Res. Commun. 313:758–764, 2004.

    Article  PubMed  CAS  Google Scholar 

  90. McBeath, R., D. M. Pirone, C. M. Nelson, K. Bhadriraju, and C. S. Chen. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev. Cell 6:483–495, 2004.

    Article  PubMed  CAS  Google Scholar 

  91. 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.

    Article  PubMed  CAS  Google Scholar 

  92. Meyer, C. J., F. J. Alenghat, P. Rim, J. H. Fong, B. Fabry, and D. E. Ingber. Mechanical control of cyclic AMP signalling and gene transcription through integrins. Nat. Cell Biol. 2:666–668, 2000.

    Article  PubMed  CAS  Google Scholar 

  93. Miller, D. C., K. M. Haberstroh, and T. J. Webster. Mechanism(s) of increased vascular cell adhesion on nanostructured poly(lactic-co-glycolic acid) films. J. Biomed. Mater. Res. A 73:476–484, 2005.

    PubMed  Google Scholar 

  94. Miller, D. C., A. Thapa, K. M. Haberstroh, and T. J. Webster. Endothelial and vascular smooth muscle cell function on poly(lactic-co-glycolic acid) with nano-structured surface features. Biomaterials 25:53–61, 2004.

    Article  PubMed  CAS  Google Scholar 

  95. Morgenthaler, S., S. Lee, S. Zurcher, and N. D. Spencer. A simple, reproducible approach to the preparation of surface-chemical gradients. Langmuir 19:10459–10462, 2003.

    Article  CAS  Google Scholar 

  96. Mrksich, M., L. E. Dike, J. Tien, D. E. Ingber, and G. M. Whitesides. Using microcontact printing to pattern the attachment of mammalian cells to self-assembled monolayers of alkanethiolates on transparent films of gold and silver. Exp. Cell Res. 235:305–313, 1997.

    Article  PubMed  CAS  Google Scholar 

  97. Mrksich, M., and G. M. Whitesides. Patterning self-assembled monolayers using microcontact printing: A new technology for biosensors? Trends Biotech. 13:228–235, 1995.

    Article  CAS  Google Scholar 

  98. Munevar, S., Y. Wang, and M. Dembo. Traction force microscopy of migrating normal and H-ras transformed 3T3 fibroblasts. Biophys. J. 80:1744–1757, 2001.

    PubMed  CAS  Google Scholar 

  99. Oberhauser, A. F., C. Badilla-Fernandez, M. Carrion-Vazquez, and J. M. Fernandez. The mechanical hierarchies of fibronectin observed with single-molecule AFM. J. Mol. Biol. 319:433–447, 2002.

    Article  PubMed  CAS  Google Scholar 

  100. Parker, K. K., A. L. Brock, C. Brangwynne, R. J. Mannix, N. Wang, E. Ostuni, N. A. Geisse, J. C. Adams, G. M. Whitesides, and D. E. Ingber. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces. Faseb. J. 16:1195–1204, 2002.

    Article  PubMed  CAS  Google Scholar 

  101. Pelham, R. J., Jr., and Y. Wang. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc. Natl. Acad. Sci. USA 94:13661–13665, 1997.

    Article  PubMed  CAS  Google Scholar 

  102. Perkins, T. T., S. R. Quake, D. E. Smith, and S. Chu. Relaxation of a single DNA molecule observed by optical microscopy. Science 264:822–826, 1994.

    PubMed  CAS  Google Scholar 

  103. Piner, R. D., J. Zhu, F. Xu, S. Hong, and C. A. Mirkin. “Dip-Pen” nanolithography. Science 283:661–663, 1999.

    Article  PubMed  CAS  Google Scholar 

  104. Plummer, S. T., Q. Wang, and P. W. Bohn. Electrochemically derived gradients of the extracellular matrix protein fibronectin on gold. Langmuir 19:7528–7536, 2003.

    Article  CAS  Google Scholar 

  105. Prime, K. L., and G. M. Whitesides. Self-assembled organic monolayers: Model systems for studying adsorption of proteins at surfaces. Science 252:1164–1167, 1991.

    PubMed  CAS  Google Scholar 

  106. Prime, K. L., and G. M. Whitesides. Adsorption of proteins onto surfaces containing end-attached oligo(ethylene oxide): A model system usings self-assembled monolayers. J. Am. Chem. Soc. 115:10714–10721, 1993.

    Article  CAS  Google Scholar 

  107. Puig-de-Morales, M., E. Millet, B. Fabry, D. Navajas, N. Wang, J. P. Butler, and J. J. Fredberg. Cytoskeletal mechanics in adherent human airway smooth muscle cells: probe specificity and scaling of protein-protein dynamics. Am. J. Physiol. Cell Physiol. 287:C643–C654, 2004.

    Article  PubMed  CAS  Google Scholar 

  108. Radmacher, M. Measuring the elastic properties of biological samples with the AFM. IEEE Eng. Med. Biol. Mag. 16:47–57, 1997.

    Article  PubMed  CAS  Google Scholar 

  109. Rajagopalan, P., W. A. Marganski, X. Q. Brown, and J. Y. Wong. Direct comparison of the spread area, contractility, and migration of balb/c 3T3 fibroblasts adhered to fibronectin- and RGD-modified substrata. Biophys. J. 87:2818–2827, 2004.

    Article  PubMed  CAS  Google Scholar 

  110. Reinhart-King, C. A., M. Dembo, and D. A. Hammer. Endothelial cell traction forces on RGD-derivatized polyacrylamide substrata. Langmuir 19:1573–1579, 2003.

    Article  CAS  Google Scholar 

  111. Reinhart-King, C. A., M. Dembo, and D. A. Hammer. The dynamics and mechanics of endothelial cell spreading. Biophys. J. 89:676–689, 2005.

    Article  PubMed  CAS  Google Scholar 

  112. Riveline, D., E. Zamir, N. Q. Balaban, U. S. Schwarz, T. Ishizaki, S. Narumiya, Z. Kam, B. Geiger, and A. D. Bershadsky. Focal contacts as mechanosensors: externally applied local mechanical force induces growth of focal contacts by an mDia1-dependent and ROCK-independent mechanism. J. Cell Biol. 153:1175–1186, 2001.

    Article  PubMed  CAS  Google Scholar 

  113. Sastry, S. K., and K. Burridge. Focal adhesions: A nexus for intracellular signaling and cytoskeletal dynamics. Exp. Cell Res. 261:25–36, 2000.

    Article  PubMed  CAS  Google Scholar 

  114. Schindler, M., I. Ahmed, J. Kamal, A. Nur-E-Kamal, T. H. Grafe, H. Young Chung, and S. Meiners. A synthetic nanofibrillar matrix promotes in vivo-like organization and morphogenesis for cells in culture. Biomaterials 26:5624–5631, 2005.

    Article  PubMed  CAS  Google Scholar 

  115. Shirinsky, V. P., A. S. Antonov, K. G. Birukov, A. V. Sobolevsky, Y. A. Romanov, N. V. Kabaeva, G. N. Antonova, and V. N. Smirnov. Mechano-chemical control of human endothelium orientation and size. J. Cell Biol. 109:331–339, 1989.

    Article  PubMed  CAS  Google Scholar 

  116. Singhvi, R., A. Kumar, G. P. Lopez, G. N. Stephanopoulos, D. I. Wang, G. M. Whitesides, and D. E. Ingber. Engineering cell shape and function. Science 264:696–698, 1994.

    PubMed  CAS  Google Scholar 

  117. Smith, J. T., J. K. Tomfohr, M. C. Wells, T. P. Beebe, Jr., T. B. Kepler, and W. M. Reichert. Measurement of cell migration on surface-bound fibronectin gradients. Langmuir 20:8279–8286, 2004.

    Article  PubMed  CAS  Google Scholar 

  118. Stopak, D., N. K. Wessells, and A. K. Harris. Morphogenetic rearrangement of injected collagen in developing chicken limb buds. Proc. Natl. Acad. Sci. USA 82:2804–2808, 1985.

    PubMed  CAS  Google Scholar 

  119. Suki, B., S. Ito, D. Stamenovic, K. R. Lutchen, and E. P. Ingenito. Biomechanics of the lung parenchyma: critical roles of collagen and mechanical forces. J. Appl. Physiol. 98:1892–1899, 2005.

    Article  PubMed  Google Scholar 

  120. Tan, J. L., W. Liu, C. M. Nelson, S. Raghavan, and C. S. Chen. Simple approach to micropattern cells on common culture substrates by tuning substrate wettability. Tissue Eng. 10:865–872, 2004.

    Article  PubMed  CAS  Google Scholar 

  121. 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. USA 100:1484–1489, 2003.

    Article  PubMed  CAS  Google Scholar 

  122. Teixeira, A. I., G. A. Abrams, P. J. Bertics, C. J. Murphy, and P. F. Nealey. Epithelial contact guidance on well-defined micro- and nanostructured substrates. J. Cell Sci. 116:1881–1892, 2003.

    Article  PubMed  CAS  Google Scholar 

  123. Teixeira, A. I., P. F. Nealey, and C. J. Murphy. Responses of human keratocytes to micro- and nanostructured substrates. J. Biomed. Mater. Res. A 71:3153–3164, 2004.

    Google Scholar 

  124. Terray, A., J. Oakey, and D. W. M. Marr. Microfluidic control using colloidal devices. Science 296:1841–1844, 2002.

    Article  PubMed  CAS  Google Scholar 

  125. Tolic-Norrelykke, I. M., and N. Wang. Traction in smooth muscle cells varies with cell spreading. J. Biomech. 38:1405–1412, 2005.

    Article  PubMed  Google Scholar 

  126. Upadhyaya, A., and M. P. Sheetz. Tension in tubulovesicular networks of Golgi and endoplasmic reticulum membranes. Biophys. J. 86:2923–2928, 2004.

    PubMed  CAS  Google Scholar 

  127. Walpita, D., and E. Hay. Studying actin-dependent processes in tissue culture. Nat. Rev. Mol. Cell Biol. 3:137–141, 2002.

    Article  PubMed  CAS  Google Scholar 

  128. Wang, N., J. P. Butler, and D. E. Ingber. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127, 1993.

    PubMed  MathSciNet  CAS  Google Scholar 

  129. Wang, H. B., M. Dembo, S. K. Hanks, and Y. Wang. Focal adhesion kinase is involved in mechanosensing during fibroblast migration. Proc. Natl. Acad. Sci. USA 98:11295–11300, 2001.

    Article  PubMed  CAS  Google Scholar 

  130. Wang, N., E. Ostuni, G. M. Whitesides, and D. E. Ingber. Micropatterning tractional forces in living cells. Cell Motil. Cytoskeleton 52:97–106, 2002.

    Article  PubMed  Google Scholar 

  131. Xia, Y., and G. M. Whitesides. Soft lithography. Annu. Rev. Mater. Sci. 28:153–184, 1998.

    Article  CAS  Google Scholar 

  132. Yim, E. K., R. M. Reano, S. W. Pang, A. F. Yee, C. S. Chen, and K. W. Leong. Nanopattern-induced changes in morphology and motility of smooth muscle cells. Biomaterials 26:5405–5413, 2005.

    Article  PubMed  CAS  Google Scholar 

  133. Yousaf, M. N., B. T. Houseman, and M. Mrksich. Using electroactive substrates to pattern the attachment of two different cell populations. Proc. Natl. Acad. Sci. USA 98:5992–5996, 2001.

    Article  PubMed  CAS  Google Scholar 

  134. Zamir, E., and B. Geiger. Molecular complexity and dynamics of cell-matrix adhesions. J. Cell Sci. 114:3583–3590, 2001.

    PubMed  CAS  Google Scholar 

  135. Zlatanova, J., S. M. Lindsay, and S. H. Leuba. Single molecule force spectroscopy in biology using the atomic force microscope. Prog. Biophys. Mol. Biol. 74:37–61, 2000.

    Article  PubMed  CAS  Google Scholar 

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ACKNOWLEDGMENTS

This work was supported in part by the National Institutes of Health (grants EB00262 and HL073305), the Department of Defense Multidisciplinary University Research Initiative, and DARPA. NS was supported by the National Institutes of Health Ruth Kirschtein National Research Service Award Postdoctoral Fellowship, and RD acknowledges support from the National Science Foundation Graduate Research Fellowship Program.

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  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    Nathan J. Sniadecki, Ravi A. Desai, Sami Alom Ruiz & Christopher S. Chen

  2. Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, 21205, USA

    Sami Alom Ruiz

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  1. Nathan J. Sniadecki
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Correspondence to Christopher S. Chen.

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Sniadecki, N.J., Desai, R.A., Ruiz, S.A. et al. Nanotechnology for Cell–Substrate Interactions. Ann Biomed Eng 34, 59–74 (2006). https://doi.org/10.1007/s10439-005-9006-3

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