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Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

  • Nanobioengineering
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An Erratum to this article was published on 27 July 2006

An Erratum to this article was published on 27 July 2006

An Erratum to this article was published on 27 July 2006

An Erratum to this article was published on 27 July 2006

Abstract

Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano- and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.

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REFERENCES

  1. 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 

  2. Alenghat, F. J., and D. E. Ingber. Mechanotransduction: All signals point to cytoskeleton, matrix, and integrins. Sci. STKE 119:PE6, 2002.

    Google Scholar 

  3. Baluska, F., and P. W. Barlow. The role of the microtubular cytoskeleton in determining nuclear chromatin structure and passage of maize root cells through the cell cycle. Eur. J. Cell Biol. 61:160–167, 1993.

    PubMed  CAS  Google Scholar 

  4. Beato, M., M. Truss, and S. Chavez. Control of transcription by steroid hormones. Ann. N. Y. Acad. Sci. 784:93–123, 1996.

    PubMed  CAS  Google Scholar 

  5. Bellin, R. M., T. W. Huiatt, D. R. Critchley, and R. M. Robson. Synemin may function to directly link muscle cell intermediate filaments to both myofibrillar z-lines and costameres. J. Biol. Chem. 276:32330–32337, 2001.

    Article  PubMed  CAS  Google Scholar 

  6. Benjamin, M., C. W. Archer, and J. R. Ralphs. Cytoskeleton of cartilage cells. Microsc. Res. Tech. 28:372–377, 1994.

    Article  PubMed  CAS  Google Scholar 

  7. Bogre, L., O. Calderini, I. Merskiene, and P. Binarova. Regulation of cell division and the cytoskeleton by mitogen-activated protein kinases in higher plants. Results Probl. Cell Differ. 27:95–117, 2000.

    PubMed  CAS  Google Scholar 

  8. Casanova, J. E. Epithelial cell cytoskeleton and intracellular trafficking v. Confluence of membrane trafficking and motility in epithelial cell models. Am. J. Physiol. Gastrointest. Liver Physiol. 283:G1015–G1019, 2002.

    PubMed  CAS  Google Scholar 

  9. 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 

  10. 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 

  11. Cole, N. B., C. L. Smith, N. Sciaky, M. Terasaki, M. Edidin, and J. Lippincott-Schwartz. Diffusional mobility of golgi proteins in membranes of living cells. Science 273:797–801, 1996.

    PubMed  CAS  Google Scholar 

  12. Costa, K. D., W. J. Hucker, and F. C. Yin. Buckling of actin stress fibers: A new wrinkle in the cytoskeletal tapestry. Cell Motil. Cytoskeleton 52:266–274, 2002.

    Article  PubMed  Google Scholar 

  13. Csermely, P. A nonconventional role of molecular chaperones: Involvement in the cytoarchitecture. News Physiol. Sci. 16:123–126, 2001.

    PubMed  CAS  Google Scholar 

  14. Csermely, P., T. Schnaider, C. Soti, Z. Prohaszka, and G. Nardai. The 90-kda molecular chaperone family: Structure, function, and clinical applications. A comprehensive review. Pharmacol. Ther. 79:129–168, 1998.

    Article  PubMed  CAS  Google Scholar 

  15. 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 

  16. de Castro, R. D., A. A. van Lammeren, S. P. Groot, R. J. Bino, and H. W. Hilhorst. Cell division and subsequent radicle protrusion in tomato seeds are inhibited by osmotic stress but DNA synthesis and formation of microtubular cytoskeleton are not. Plant Physiol. 122:327–336, 2000.

    Article  PubMed  Google Scholar 

  17. Dekker, R. J., S. van Soest, R. D. Fontijn, S. Salamanca, P. G. de Groot, E. VanBavel, H. Pannekoek, and A. J. Horrevoet. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung kruppel-like factor (klf2). Blood 100:1689–1698, 2002.

    Article  PubMed  CAS  Google Scholar 

  18. Desai, T. A. Microfabrication technology for pancreatic cell encapsulation. Expert Opin. Biol. Ther. 2:633–646, 2002.

    Article  PubMed  CAS  Google Scholar 

  19. Engstrom, K. G., and H. J. Meiselman. Combined use of micropipette aspiration and perifusion for studying red blood cell volume regulation. Cytometry 27:345–352, 1997.

    Article  PubMed  CAS  Google Scholar 

  20. Farinas, J., A. W. Chow, and H. G. Wada. A microfluidic device for measuring cellular membrane potential. Anal. Biochem. 295:138–142, 2001.

    Article  PubMed  CAS  Google Scholar 

  21. Fath, K. R., S. N. Mamajiwalla, and D. R. Burgess. The cytoskeleton in development of epithelial cell polarity. J. Cell Sci. 17 (Suppl.):65–73, 1993.

    Google Scholar 

  22. Ferrer, I., R. Blanco, M. Carmona, B. Puig, M. Barrachina, C. Gomez, and S. Ambrosio. Active, phosphorylation-dependent mitogen-activated protein kinase (mapk/erk), stress-activated protein kinase/c-jun n-terminal kinase (sapk/jnk), and p38 kinase expression in parkinson's disease and dementia with lewy bodies. J. Neural Transm. 108:1383–1396, 2001.

    Article  PubMed  CAS  Google Scholar 

  23. Fleming, T. P., P. M. Cannon, and S. J. Pickering. The cytoskeleton, endocytosis and cell polarity in the mouse preimplantation embryo. Dev. Biol. 113:406–419, 1986.

    Article  PubMed  CAS  Google Scholar 

  24. Fluck, M., J. A. Carson, S. E. Gordon, A. Ziemiecki, and F. W. Booth. Focal adhesion proteins fak and paxillin increase in hypertrophied skeletal muscle. Am. J. Physiol. 277:C152–C162, 1999.

    PubMed  CAS  Google Scholar 

  25. Folch, A., and M. Toner. Cellular micropatterns on biocompatible materials. Biotechnol. Prog. 14:388–392, 1998.

    Article  PubMed  CAS  Google Scholar 

  26. Fox, J. A., T. E. Hotaling, C. Struble, J. Ruppel, D. J. Bates, and M. B. Schoenhoff. Tissue distribution and complex formation with ige of an anti-ige antibody after intravenous administration in cynomolgus monkeys. J. Pharmacol. Exp. Ther. 279:1000–1008, 1996.

    PubMed  CAS  Google Scholar 

  27. Freitas, R. A. Jr. Exploratory design in medical nanotechnology: A mechanical artificial red cell. Artif. Cells Blood Substit. Immobil. Biotechnol. 26:411–430, 1998.

    Article  PubMed  CAS  Google Scholar 

  28. Fu, A. Y., H. P. Chou, C. Spence, F. H. Arnold, and S. R. Quake. An integrated microfabricated cell sorter. Anal. Chem. 74:2451–2457, 2002.

    Article  PubMed  CAS  Google Scholar 

  29. Galigniana, M. D., J. L. Scruggs, J. Herrington, M. J. Welsh, C. Carter-Su, P. R. Housley, and W. B. Pratt. Heat shock protein 90-dependent (geldanamycin-inhibited) movement of the glucocorticoid receptor through the cytoplasm to the nucleus requires intact cytoskeleton. Mol. Endocrinol. 12:1903–1913, 1998.

    Article  PubMed  CAS  Google Scholar 

  30. Gao, X., Y. Cui, R. M. Levenson, L. W. Chung, and S. Nie. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22:969–976, 2004.

    Article  PubMed  CAS  Google Scholar 

  31. Garcia-Cardena, G., J. I. Comander, B. R. Blackman, K. R. Anderson, and M. A. Gimbrone. Mechanosensitive endothelial gene expression profiles: Scripts for the role of hemodynamics in atherogenesis? Ann. N. Y. Acad. Sci. 947:1–6, 2001.

    Article  PubMed  CAS  Google Scholar 

  32. Hable, W. E., and D. L. Kropf. Roles of secretion and the cytoskeleton in cell adhesion and polarity establishment in pelvetia compressa zygotes. Dev. Biol. 198:45–56, 1998.

    PubMed  CAS  Google Scholar 

  33. Hasezawa, S., and F. Kumagai. Dynamic changes and the role of the cytoskeleton during the cell cycle in higher plant cells. Int. Rev. Cytol. 214:161–191, 2002.

    PubMed  CAS  Google Scholar 

  34. Helmke, B. P., and P. F. Davies. The cytoskeleton under external fluid mechanical forces: Hemodynamic forces acting on the endothelium. Ann. Biomed. Eng. 30:284–296, 2002.

    Article  PubMed  Google Scholar 

  35. 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.

    PubMed  CAS  Google Scholar 

  36. Holth, L. T., D. N. Chadee, V. A. Spencer, S. K. Samuel, J. R. Safneck, and J. R. Davie. Chromatin, nuclear matrix and the cytoskeleton: Role of cell structure in neoplastic transformation (review). Int. J. Oncol. 13:827–837, 1998.

    PubMed  CAS  Google Scholar 

  37. Htun, H., J. Barsony, I. Renyi, D. L. Gould, and G. L. Hager. Visualization of glucocorticoid receptor translocation and intranuclear organization in living cells with a green fluorescent protein chimera. Proc. Natl. Acad. Sci. U.S.A. 93:4845–4850, 1996.

    Article  PubMed  CAS  Google Scholar 

  38. Htun, H., L. T. Holth, D. Walker, J. R. Davie, and G. L. Hager. Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor. Mol. Biol. Cell 10:471–486, 1999.

    PubMed  CAS  Google Scholar 

  39. 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 

  40. Hu, J., Z. H. Wang, and Z. L. Tao. Micropatterning of biotin-avidin layers and cell location. Sheng Wu Gong Cheng Xue Bao 18:619–621, 2002.

    PubMed  CAS  Google Scholar 

  41. Huang, S., and D. E. Ingber. A discrete cell cycle checkpoint in late g(1) that is cytoskeleton-dependent and map kinase (erk)-independent. Exp. Cell Res. 275:255–264, 2002.

    Article  PubMed  CAS  Google Scholar 

  42. Huang, Y., E. L. Mather, J. L. Bell, and M. Madou. Mems-based sample preparation for molecular diagnostics. Anal. Bioanal. Chem. 372:49–65, 2002.

    Article  PubMed  CAS  Google Scholar 

  43. Huen, A. C., J. K. Park, L. M. Godsel, X. Chen, L. J. Bannon, E. V. Amarg, T. Y. Hudson, A. K. Mongiu, I. M. Leigh, D. Kelsell, B. M. Gumbiner, and K. J. Green. Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength. J. Cell Biol. 159:1005–1017, 2002.

    Article  PubMed  CAS  Google Scholar 

  44. Hutcheson, I. R., and T. M. Griffith. Mechanotransduction through the endothelial cytoskeleton: Mediation of flow- but not agonist-induced edrf release. Br. J. Pharmacol. 118:720–726, 1996.

    PubMed  CAS  Google Scholar 

  45. Ishikawa, H. Cell polarity and cytoskeleton. Tanpakushitsu Kakusan Koso 34:1742–1748, 1989.

    PubMed  CAS  Google Scholar 

  46. Izutsu, K. Cell division and the microtubular cytoskeleton. Hum. Cell 4:100–108, 1991.

    PubMed  CAS  Google Scholar 

  47. Kaibuchi, K., S. Kuroda, and M. Amano. Regulation of the cytoskeleton and cell adhesion by the rho family gtpases in mammalian cells. Annu. Rev. Biochem. 68:459–486, 1999.

    Article  PubMed  CAS  Google Scholar 

  48. Kane, R. S., S. Takayama, E. Ostuni, D. E. Ingber, and G. M. Whitesides. Patterning proteins and cells using soft lithography. Biomaterials 20:2363–2376, 1999.

    Article  PubMed  CAS  Google Scholar 

  49. Kano, Y., K. Katoh, and K. Fujiwara. Lateral zone of cell–cell adhesion as the major fluid shear stress-related signal transduction site. Circ. Res. 86:425–433, 2000.

    PubMed  CAS  Google Scholar 

  50. Kataoka, N., K. Iwaki, K. Hashimoto, S. Mochizuki, Y. Ogasawara, M. Sato, K. Tsujioka, and F. Kajiya. Measurements of endothelial cell-to-cell and cell-to-substrate gaps and micromechanical properties of endothelial cells during monocyte adhesion. Proc. Natl. Acad. Sci. U.S.A. 99:15638–15643, 2002.

    Article  PubMed  CAS  Google Scholar 

  51. Kenis, P. J., R. F. Ismagilov, and G. M. Whitesides. Microfabrication inside capillaries using multiphase laminar flow patterning. Science 285:83–85, 1999.

    Article  PubMed  CAS  Google Scholar 

  52. Kubicek, J. D., S. Brelsford, P. Ahluwalia, and P. R. Leduc. Integrated lithographic membranes and surface adhesion chemistry for three-dimensional cellular stimulation. Langmuir 20:11552–11556, 2004.

    Article  PubMed  CAS  Google Scholar 

  53. Kural, C., H. Kim, S. Syed, G. Goshima, V. I. Gelfand, and P. R. Selvin. Kinesin and dynein move a peroxisome in vivo: A tug-of-war or coordinated movement? Science 308:1469–1472, 2005.

    Article  PubMed  CAS  Google Scholar 

  54. LeDuc, P., C. Haber, G. Bao, and D. Wirtz. Dynamics of individual flexible polymers in a shear flow. Nature 399:564–566, 1999.

    Article  PubMed  CAS  Google Scholar 

  55. LeDuc, P., E. Ostuni, G. Whitesides, and D. Ingber. Use of micropatterned adhesive surfaces for control of cell behavior. Methods Cell Biol. 69:385–401, 2002.

    Article  PubMed  CAS  Google Scholar 

  56. Li, C., Y. Hu, M. Mayr, and Q. Xu. Cyclic strain stress-induced mitogen-activated protein kinase (mapk) phosphatase 1 expression in vascular smooth muscle cells is regulated by ras/rac-mapk pathways. J. Biol. Chem. 274:25273–25280, 1999.

    Article  PubMed  CAS  Google Scholar 

  57. Li, Y. Q., A. Moscatelli, G. Cai, and M. Cresti. Functional interactions among cytoskeleton, membranes, and cell wall in the pollen tube of flowering plants. Int. Rev. Cytol. 176:133–199, 1997.

    Article  PubMed  CAS  Google Scholar 

  58. Li Jeon, N., 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. Biotechnol. 20:826–830, 2002.

    PubMed  CAS  Google Scholar 

  59. Liu, J., Q. Zhang, E. E. Remsen, and K. L. Wooley. Nanostructured materials designed for cell binding and transduction. Biomacromolecules 2:362–368, 2001.

    Article  PubMed  CAS  Google Scholar 

  60. Machesky, L. M., and J. A. Cooper. Cell motility. Bare bones of the cytoskeleton. Nature 401:542–543, 1999.

    Article  PubMed  CAS  Google Scholar 

  61. Malek, A. M., and S. Izumo. Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. J. Cell Sci. 109(Pt 4):713–726, 1996.

    PubMed  CAS  Google Scholar 

  62. Maniotis, A. J., K. Bojanowski, and D. E. Ingber. Mechanical continuity and reversible chromosome disassembly within intact genomes removed from living cells. J. Cell. Biochem. 65:114–130, 1997.

    Article  PubMed  CAS  Google Scholar 

  63. 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. U.S.A. 94:849–854, 1997.

    Article  PubMed  CAS  Google Scholar 

  64. Matsuda, T., K. Inoue, and T. Sugawara. Development of micropatterning technology for cultured cells. ASAIO Trans. 36:M559–M562, 1990.

    PubMed  CAS  Google Scholar 

  65. 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 

  66. Miller, C., S. Jeftinija, and S. Mallapragada. Micropatterned schwann cell-seeded biodegradable polymer substrates significantly enhance neurite alignment and outgrowth. Tissue Eng. 7:705–715, 2001.

    Article  PubMed  CAS  Google Scholar 

  67. Miller, C., H. Shanks, A. Witt, G. Rutkowski, and S. Mallapragada. Oriented schwann cell growth on micropatterned biodegradable polymer substrates. Biomaterials 22:1263–1269, 2001.

    Article  PubMed  CAS  Google Scholar 

  68. Minton, A. P. Implications of macromolecular crowding for protein assembly. Curr. Opin. Struct. Biol. 10:34–39, 2000.

    Article  PubMed  CAS  Google Scholar 

  69. Minton, A. P. The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J. Biol. Chem. 276:10577–10580, 2001.

    Article  PubMed  CAS  Google Scholar 

  70. Moon, J. J., M. Matsumoto, S. Patel, L. Lee, J. L. Guan, and S. Li. Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction. J. Cell. Physiol. 203:166–176, 2004.

    Article  CAS  Google Scholar 

  71. Morimoto, N., R. M. Raphael, A. Nygren, and W. E. Brownell. Excess plasma membrane and effects of ionic amphipaths on mechanics of outer hair cell lateral wall. Am. J. Physiol. Cell Physiol. 282:C1076–C1086, 2002.

    PubMed  CAS  Google Scholar 

  72. Nelson, W. J., R. W. Hammerton, A. Z. Wang, and E. M. Shore. Involvement of the membrane-cytoskeleton in development of epithelial cell polarity. Semin. Cell Biol. 1:359–371, 1990.

    PubMed  CAS  Google Scholar 

  73. Ogawa, H., S. Inouye, F. I. Tsuji, K. Yasuda, and K. Umesono. Localization, trafficking, and temperature-dependence of the aequorea green fluorescent protein in cultured vertebrate cells. Proc. Natl. Acad. Sci. U.S.A. 92:11899–11903, 1995.

    PubMed  CAS  Google Scholar 

  74. Parry, G., J. C. Beck, L. Moss, J. Bartley, and G. K. Ojakian. Determination of apical membrane polarity in mammary epithelial cell cultures: The role of cell–cell, cell–substratum, and membrane–cytoskeleton interactions. Exp. Cell Res. 188:302–311, 1990.

    Article  PubMed  CAS  Google Scholar 

  75. Patel, N., R. Bhandari, K. M. Shakesheff, S. M. Cannizzaro, M. C. Davies, R. Langer, C. J. Roberts, S. J. Tendler, and P. M. Williams. Printing patterns of biospecifically-adsorbed protein. J. Biomater. Sci. Polym. Ed. 11:319–331, 2000.

    Article  PubMed  CAS  Google Scholar 

  76. Plopper, G., and D. E. Ingber. Rapid induction and isolation of focal adhesion complexes. Biochem. Biophys. Res. Commun. 193:571–578, 1993.

    Article  PubMed  CAS  Google Scholar 

  77. Pollack, G. Cells, Gels, and the Engines of Life. Seattle, WA: Ebner, 2001

    Google Scholar 

  78. Prima, V., C. Depoix, B. Masselot, P. Formstecher, and P. Lefebvre. Alteration of the glucocorticoid receptor subcellular localization by non steroidal compounds. J. Steroid Biochem. Mol. Biol. 72:1–12, 2000.

    Article  PubMed  CAS  Google Scholar 

  79. Puskar, K., L. Apelstein, S. Ta'asan, R. Schwartz, and P. LeDuc. Understanding actin organization in cell structure through lattice based monte carlo simulations. MCB 1:123–132, 2004.

    PubMed  Google Scholar 

  80. Quake, S. R., and A. Scherer. From micro- to nanofabrication with soft materials. Science 290:1536–1540, 2000.

    Article  PubMed  CAS  Google Scholar 

  81. Reipert, S., F. Steinbock, I. Fischer, R. E. Bittner, A. Zeold, and G. Wiche. Association of mitochondria with plectin and desmin intermediate filaments in striated muscle. Exp. Cell Res. 252:479–491, 1999.

    Article  PubMed  CAS  Google Scholar 

  82. Resnick, N., H. Yahav, L. M. Khachigian, T. Collins, K. R. Anderson, F. C. Dewey, and M. A. Gimbrone. Endothelial gene regulation by laminar shear stress. Adv. Exp. Med. Biol. 430:155–164, 1997.

    PubMed  CAS  Google Scholar 

  83. Rivas, G., J. A. Fernandez, and A. P. Minton. Direct observation of the enhancement of noncooperative protein self-assembly by macromolecular crowding: Indefinite linear self-association of bacterial cell division protein ftsz. Proc. Natl. Acad. Sci. U.S.A. 98:3150–3155, 2001.

    Article  PubMed  CAS  Google Scholar 

  84. Rivero, F., B. Koppel, B. Peracino, S. Bozzaro, F. Siegert, C. J. Weijer, M. Schleicher, R. Albrecht, and A. A. Noegel. The role of the cortical cytoskeleton: F-actin crosslinking proteins protect against osmotic stress, ensure cell size, cell shape and motility, and contribute to phagocytosis and development. J. Cell Sci. 109(Pt 11):2679–2691, 1996.

    PubMed  CAS  Google Scholar 

  85. Salter, D. M., S. J. Millward-Sadler, G. Nuki, and M. O. Wright. Integrin-interleukin-4 mechanotransduction pathways in human chondrocytes. Clin. Orthop. S49–S60, 2001.

  86. Sanger, J. W., and J. M. Sanger. The cytoskeleton and cell division. Methods Achiev. Exp. Pathol. 8:110–142, 1979.

    PubMed  CAS  Google Scholar 

  87. Schnittler, H. J., S. W. Schneider, H. Raifer, F. Luo, P. Dieterich, I. Just, and K. Aktories. Role of actin filaments in endothelial cell–cell adhesion and membrane stability under fluid shear stress. Pflugers Arch. 442:675–687, 2001.

    Article  PubMed  CAS  Google Scholar 

  88. Shafrir, Y., and G. Forgacs. Mechanotransduction through the cytoskeleton. Am. J. Physiol. Cell Physiol. 282:C479–C486, 2002.

    PubMed  CAS  Google Scholar 

  89. Shen, N., D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur. Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor. Mech. Chem. Biosyst. 2:17–25, 2005.

    PubMed  Google Scholar 

  90. Shrode, L. D., E. A. Rubie, J. R. Woodgett, and S. Grinstein. Cytosolic alkalinization increases stress-activated protein kinase/c-jun nh2-terminal kinase (sapk/jnk) activity and p38 mitogen-activated protein kinase activity by a calcium-independent mechanism. J. Biol. Chem. 272:13653–13659, 1997.

    Article  PubMed  CAS  Google Scholar 

  91. Silverstein, R. L., L. L. Leung, P. C. Harpel, and R. L. Nachman. Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator. J. Clin. Invest. 74:1625–1633, 1984.

    PubMed  CAS  Google Scholar 

  92. 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 

  93. Small, J. V., and M. Gimona. The cytoskeleton of the vertebrate smooth muscle cell. Acta Physiol. Scand. 164:341–348, 1998.

    Article  PubMed  CAS  Google Scholar 

  94. Small, J. V., I. Kaverina, O. Krylyshkina, and K. Rottner. Cytoskeleton cross-talk during cell motility. FEBS Lett. 452:96–99, 1999.

    Article  PubMed  CAS  Google Scholar 

  95. Soll, D. R. Researchers in cell motility and the cytoskeleton can play major roles in understanding aids. Cell Motil. Cytoskeleton 37:91–97, 1997.

    Article  PubMed  CAS  Google Scholar 

  96. Spector, A. A., M. Ameen, P. G. Charalambides, and A. S. Popel. Nanostructure, effective properties, and deformation pattern of the cochlear outer hair cell cytoskeleton. J. Biomech. Eng. 124:180–187, 2002.

    Article  PubMed  Google Scholar 

  97. Steinbock, F. A., and G. Wiche. Plectin: A cytolinker by design. Biol. Chem. 380:151–158, 1999.

    Article  PubMed  CAS  Google Scholar 

  98. Streiblova, E., and J. Hasek. Role of the cytoskeleton and homologs of retrovirus genes in yeast cell division. Izv. Akad. Nauk SSSR Biol. 353–360, 1987.

  99. Svoboda, A., I. Slaninova, and A. Holubarova. Cytoskeleton in regenerating protoplasts and restoration of cell polarity in the yeast saccharomyces cerevisiae. Acta Biol. Hung. 52:325–333, 2001.

    Article  PubMed  CAS  Google Scholar 

  100. Takayama, S., E. Ostuni, P. LeDuc, K. Naruse, D. E. Ingber, and G. M. Whitesides. Subcellular positioning of small molecules. Nature 411:1016, 2001.

    Article  PubMed  CAS  Google Scholar 

  101. Takayama, S., E. Ostuni, P. LeDuc, K. Naruse, D. E. Ingber, and G. M. Whitesides. Selective chemical treatment of cellular microdomains using multiple laminar streams. Chem. Biol. 10:123–130, 2003.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  103. Thiebaud, P., L. Lauer, W. Knoll, and A. Offenhausser. Pdms device for patterned application of microfluids to neuronal cells arranged by microcontact printing. Biosens. Bioelectron. 17:87–93, 2002.

    Article  PubMed  CAS  Google Scholar 

  104. Tien, J., C. M. Nelson, and C. S. Chen. Fabrication of aligned microstructures with a single elastomeric stamp. Proc. Natl. Acad. Sci. U.S.A. 99:1758–1762, 2002.

    Article  PubMed  CAS  Google Scholar 

  105. Topper, J. N., and M. A. Gimbrone Jr. Blood flow and vascular gene expression: Fluid shear stress as a modulator of endothelial phenotype. Mol. Med. Today 5:40–46, 1999.

    Article  PubMed  CAS  Google Scholar 

  106. Truskey, G. A., and J. S. Pirone. The effect of fluid shear stress upon cell adhesion to fibronectin-treated surfaces. J. Biomed. Mater. Res. 24:1333–1353, 1990.

    Article  PubMed  CAS  Google Scholar 

  107. Tsai, M. J., and B. W. O'Malley. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem. 63:451–486, 1994.

    Article  PubMed  CAS  Google Scholar 

  108. Tumlin, J. A., J. P. Lea, C. E. Swanson, C. L. Smith, S. S. Edge, and J. S. Someren. Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins. J. Clin. Invest. 99:1217–1223, 1997.

    Article  PubMed  CAS  Google Scholar 

  109. Vale, R. D., and R. A. Milligan. The way things move: Looking under the hood of molecular motor proteins. Science 288:88–95, 2000.

    Article  PubMed  CAS  Google Scholar 

  110. van Kooten, T. G., J. M. Schakenraad, H. C. van der Mei, A. Dekker, C. J. Kirkpatrick, and H. J. Busscher. Fluid shear induced endothelial cell detachment from glass—influence of adhesion time and shear stress. Med. Eng. Phys. 16:506–512, 1994.

    PubMed  Google Scholar 

  111. Wallrabe, U., P. Ruther, T. Schaller, and W. K. Schomburg. Microsystems in medicine. Int. J. Artif. Organs 21:137–146, 1998.

    PubMed  CAS  Google Scholar 

  112. 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 

  113. Wang, J. H., P. Goldschmidt-Clermont, J. Wille, and F. C. Yin. Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J. Biomech. 34:1563–1572, 2001.

    Article  PubMed  CAS  Google Scholar 

  114. Wang, N., and D. E. Ingber. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys. J. 66:2181–2189, 1994.

    Article  PubMed  CAS  Google Scholar 

  115. Whitesell, L., E. G. Mimnaugh, B. de Costa, C. E. Myers, and L. M. Neckers. Inhibition of heat shock protein hsp90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: Essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. U.S.A. 91:8324–8328, 1994.

    PubMed  CAS  Google Scholar 

  116. Williams, B. Mechanical influences on vascular smooth muscle cell function. J. Hypertens. 16:1921–1929, 1998.

    Article  PubMed  CAS  Google Scholar 

  117. Williams, S. E., I. Valenzuela, A. S. Kadish, and K. M. Das. Glomerular immune complex formation and induction of lymphoma in athymic nude mice by tissue filtrates of crohn's disease patients. J. Lab. Clin. Med. 99:827–837, 1982.

    PubMed  CAS  Google Scholar 

  118. Wozniak, M., A. Fausto, C. P. Carron, D. M. Meyer, and K. A. Hruska. Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression. J. Bone Miner. Res. 15:1731–1745, 2000.

    PubMed  CAS  Google Scholar 

  119. Xu, C. W. High-density cell microarrays for parallel functional determinations. Genome Res. 12:482–486, 2002.

    PubMed  CAS  Google Scholar 

  120. Yanagi, S., N. Shimbara, and T. Tamura. Tissue and cell distribution of a mammalian proteasomal atpase, mss1, and its complex formation with the basal transcription factors. Biochem. Biophys. Res. Commun. 279:568–573, 2000.

    Article  PubMed  CAS  Google Scholar 

  121. Yang, F., and Y. H. Li. Roles of integrins and cytoskeleton in cellular mechanotransduction. Space Med. Med. Eng. (Beijing) 15:309–312, 2002.

    Google Scholar 

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ACKNOWLEDGMENTS

This work was supported in part by grants from the National Science Foundation (R.B.), National Science Foundation-CAREER (P.L.), Pennsylvania Infrastructure Technology Alliance, and the Department of Energy-Genome to Life Program. The authors would also like to thank M. L. Ledbetter, S. LeDuc, S. Lawrence, and W. Messner for their helpful discussions and input on the manuscript.

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Correspondence to Philip P. LeDuc.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10439-006-9137-1

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LeDuc, P.P., Bellin, R.R. Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior. Ann Biomed Eng 34, 102–113 (2006). https://doi.org/10.1007/s10439-005-9008-1

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