1932

Abstract

Cells need to be anchored to extracellular matrix (ECM) to survive, yet the role of ECM in guiding developmental processes, tissue homeostasis, and aging has long been underestimated. How ECM orchestrates the deterioration of healthy to pathological tissues, including fibrosis and cancer, also remains poorly understood. Inquiring how alterations in ECM fiber tension might drive these processes is timely, as mechanobiology is a rapidly growing field, and many novel mechanisms behind the mechanical forces that can regulate protein, cell, and tissue functions have recently been deciphered. The goal of this article is to review how forces can switch protein functions, and thus cell signaling, and thereby inspire new approaches to exploit the mechanobiology of ECM in regenerative medicine as well as for diagnostic and therapeutic applications. Some of the mechanochemical switching concepts described here for ECM proteins are more general and apply to intracellular proteins as well.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-021317-121312
2018-02-10
2024-06-19
Loading full text...

Full text loading...

/deliver/fulltext/physiol/80/1/annurev-physiol-021317-121312.html?itemId=/content/journals/10.1146/annurev-physiol-021317-121312&mimeType=html&fmt=ahah

Literature Cited

  1. Zanconato F, Cordenonsi M, Piccolo S. 1.  2016. YAP/TAZ at the roots of cancer. Cancer Cell 29:783–803 [Google Scholar]
  2. Shivashankar GV, Sheetz M, Matsudaira P. 2.  2015. Mechanobiology. Integr. Biol. 7:1091–92 [Google Scholar]
  3. Paluch EK, Discher DE. 3.  2015. Cell motion and mechanobiology. Mol. Biol. Cell 26:1011 [Google Scholar]
  4. Swift J, Ivanovska IL, Buxboim A, Harada T, Dingal PC. 4.  et al. 2013. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341:1240104 [Google Scholar]
  5. Janmey PA, Wells RG, Assoian RK, McCulloch CA. 5.  2013. From tissue mechanics to transcription factors. Differentiation 86:112–20 [Google Scholar]
  6. Winograd-Katz SE, Fassler R, Geiger B, Legate KR. 6.  2014. The integrin adhesome: from genes and proteins to human disease. Nat. Rev. Mol. Cell Biol. 15:273–88 [Google Scholar]
  7. Sun Z, Guo SS, Fässler R. 7.  2016. Integrin-mediated mechanotransduction. J. Cell Biol. 215:445–56 [Google Scholar]
  8. Piccolo S.8.  2013. Developmental biology: mechanics in the embryo. Nature 504:223–25 [Google Scholar]
  9. Schoen I, Pruitt BL, Vogel V. 9.  2013. The yin-yang in rigidity sensing: how forces and mechanical properties regulate the cellular response to materials. Annu. Rev. Mat. Sci. 43:589–618 [Google Scholar]
  10. Iskratsch T, Wolfenson H, Sheetz MP. 10.  2014. Appreciating force and shape-the rise of mechanotransduction in cell biology. Nat. Rev. Mol. Cell Biol. 15:825–33 [Google Scholar]
  11. Schwarzbauer JE, DeSimone DW. 11.  2011. Fibronectins, their fibrillogenesis, and in vivo functions. Cold Spring Harb. Perspect. Biol. 3:a005041 [Google Scholar]
  12. Van De Water L Varney S, Tomasek JJ. 12.  2013. Mechanoregulation of the myofibroblast in wound contraction, scarring, and fibrosis: opportunities for new therapeutic intervention. Adv. Wound Care 2:122–41 [Google Scholar]
  13. Carver W, Goldsmith EC. 13.  2013. Regulation of tissue fibrosis by the biomechanical environment. Biomed. Res. Int. 2013:101979 [Google Scholar]
  14. Wong VW, Rustad KC, Akaishi S, Sorkin M, Glotzbach JP. 14.  et al. 2011. Focal adhesion kinase links mechanical force to skin fibrosis via inflammatory signaling. Nat. Med. 18:148–52 [Google Scholar]
  15. Rybinski B, Franco-Barraza J, Cukierman E. 15.  2014. The wound healing, chronic fibrosis, and cancer progression triad. Physiol. Genom. 46:223–44 [Google Scholar]
  16. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M. 16.  et al. 2009. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139:891–906 [Google Scholar]
  17. Kai F, Laklai H, Weaver VM. 17.  2016. Force matters: biomechanical regulation of cell invasion and migration in disease. Trends Cell Biol 26:486–97 [Google Scholar]
  18. Chaudhuri O, Koshy ST, Branco da Cunha C, Shin JW, Verbeke CS. 18.  et al. 2014. Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat. Mater. 13:970–78 [Google Scholar]
  19. Van Obberghen-Schilling E, Tucker RP, Saupe F, Gasser I, Cseh B, Orend G. 19.  2011. Fibronectin and tenascin-C: accomplices in vascular morphogenesis during development and tumor growth. Int. J. Dev. Biol. 55:511–25 [Google Scholar]
  20. Wijelath ES, Rahman S, Namekata M, Murray J, Nishimura T. 20.  et al. 2006. Heparin-II domain of fibronectin is a vascular endothelial growth factor-binding domain: enhancement of VEGF biological activity by a singular growth factor/matrix protein synergism. Circ. Res. 99:853–60 [Google Scholar]
  21. Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA. 21.  2013. Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. PNAS 110:4563–8 [Google Scholar]
  22. Zhu J, Clark RA. 22.  2014. Fibronectin at select sites binds multiple growth factors and enhances their activity: expansion of the collaborative ECM-GF paradigm. J. Investig. Dermatol. 134:895–901 [Google Scholar]
  23. Martino MM, Briquez PS, Guc E, Tortelli F, Kilarski WW. 23.  et al. 2014. Growth factors engineered for super-affinity to the extracellular matrix enhance tissue healing. Science 343:885–88 [Google Scholar]
  24. Hinz B.24.  2015. The extracellular matrix and transforming growth factor-β1: tale of a strained relationship. Matrix Biol 47:54–65 [Google Scholar]
  25. Hynes RO.25.  2009. The extracellular matrix: not just pretty fibrils. Science 326:1216–19 [Google Scholar]
  26. Provenzano PP, Keely PJ. 26.  2011. Mechanical signaling through the cytoskeleton regulates cell proliferation by coordinated focal adhesion and Rho GTPase signaling. J. Cell Sci. 124:1195–205 [Google Scholar]
  27. Leight JL, Liu WF, Chaturvedi RR, Chen S, Yang MT. 27.  et al. 2012. Manipulation of 3D cluster size and geometry by release from 2D micropatterns. Cell. Mol. Bioeng. 5:299–306 [Google Scholar]
  28. Duscher D, Maan ZN, Wong VW, Rennert RC, Januszyk M. 28.  et al. 2014. Mechanotransduction and fibrosis. J. Biomech. 47:1997–2005 [Google Scholar]
  29. DuFort CC, Paszek MJ, Weaver VM. 29.  2011. Balancing forces: architectural control of mechanotransduction. Nat. Rev. Mol. Cell Biol. 12:308–19 [Google Scholar]
  30. Humphrey JD, Dufresne ER, Schwartz MA. 30.  2014. Mechanotransduction and extracellular matrix homeostasis. Nat. Rev. Mol. Cell Biol. 15:802–12 [Google Scholar]
  31. Vogel V.31.  2006. Mechanotransduction involving multimodular proteins: converting force into biochemical signals. Annu. Rev. Biophys. Biomol. Struct. 35:459–88 [Google Scholar]
  32. Arnoldini S, Moscaroli A, Chabria M, Hilbert M, Hertig S. 32.  et al. Novel peptide probes to assess the tensional state of fibronectin fibers in tissue. Nat. Commun 8:1793 [Google Scholar]
  33. Hubbell JA, Langer R. 33.  2013. Translating materials design to the clinic. Nat. Mater. 12:963–66 [Google Scholar]
  34. Guthold M, Liu W, Sparks EA, Jawerth LM, Peng L. 34.  et al. 2007. A comparison of the mechanical and structural properties of fibrin fibers with other protein fibers. Cell Biochem. Biophys. 49:165–81 [Google Scholar]
  35. Liu W, Jawerth LM, Sparks EA, Falvo MR, Hantgan RR. 35.  et al. 2006. Fibrin fibers have extraordinary extensibility and elasticity. Science 313:634 [Google Scholar]
  36. Klotzsch E, Smith ML, Kubow KE, Muntwyler S, Little WC. 36.  et al. 2009. Fibronectin forms the most extensible biological fibers displaying switchable force-exposed cryptic binding sites. PNAS 106:18267–72 [Google Scholar]
  37. Hocking DC, Sottile J, McKeown-Longo PJ. 37.  1994. Fibronectin's III-1 module contains a conformation-dependent binding site for the amino-terminal region of fibronectin. J. Biol. Chem. 269:19183–87 [Google Scholar]
  38. Ingham KC, Brew SA, Huff S, Litvinovich SV. 38.  1997. Cryptic self-association sites in type III modules of fibronectin. J. Biol. Chem. 272:1718–24 [Google Scholar]
  39. Zhong C, Chrzanowska-Wodnicka M, Brown J, Shaub A, Belkin AM, Burridge K. 39.  1998. Rho-mediated contractility exposes a cryptic site in fibronectin and induces fibronectin matrix assembly. J. Cell Biol. 141:539–51 [Google Scholar]
  40. Langenbach KJ, Sottile J. 40.  1999. Identification of protein-disulfide isomerase activity in fibronectin. J. Biol. Chem. 274:7032–38 [Google Scholar]
  41. Little WC, Smith ML, Ebneter U, Vogel V. 41.  2008. Assay to mechanically tune and optically probe fibrillar fibronectin conformations from fully relaxed to breakage. Matrix Biol 27:451–61 [Google Scholar]
  42. Adhikari AS, Glassey E, Dunn AR. 42.  2012. Conformational dynamics accompanying the proteolytic degradation of trimeric collagen I by collagenases. J. Am. Chem. Soc. 134:13259–65 [Google Scholar]
  43. Chabria M, Hertig S, Smith ML, Vogel V. 43.  2010. Stretching fibronectin fibres disrupts binding of bacterial adhesins by physically destroying an epitope. Nat. Commun. 1:135 [Google Scholar]
  44. Kubow KE, Vukmirovic R, Zhe L, Klotzsch E, Smith ML. 44.  et al. 2015. Mechanical forces regulate the interactions of fibronectin and collagen I in extracellular matrix. Nat. Commun. 6:8026 [Google Scholar]
  45. Ginsberg M, Pierschbacher MD, Ruoslahti E, Marguerie G, Plow E. 45.  1985. Inhibition of fibronectin binding to platelets by proteolytic fragments and synthetic peptides which support fibroblast adhesion. J. Biol. Chem. 260:3931–36 [Google Scholar]
  46. Kato R, Ishikawa T, Kamiya S, Oguma F, Ueki M. 46.  et al. 2002. A new type of antimetastatic peptide derived from fibronectin. Clin. Cancer Res. 8:2455–62 [Google Scholar]
  47. Ding L, Guo D, Homandberg GA. 47.  2009. Fibronectin fragments mediate matrix metalloproteinase upregulation and cartilage damage through proline rich tyrosine kinase 2, c-src, NF-κB and protein kinase Cδ. Osteoarthr. Cartilage 17:1385–92 [Google Scholar]
  48. Joshi R, Goihberg E, Ren W, Pilichowska M, Mathew P. 48.  2016. Proteolytic fragments of fibronectin function as matrikines driving the chemotactic affinity of prostate cancer cells to human bone marrow mesenchymal stromal cells via the α5β1 integrin. Cell Adh. Migr.1–11 [Google Scholar]
  49. Londono R, Badylak SF. 49.  2015. Biologic scaffolds for regenerative medicine: mechanisms of in vivo remodeling. Ann. Biomed. Eng. 43:577–92 [Google Scholar]
  50. Hinz B.50.  2016. The role of myofibroblasts in wound healing. Curr. Res. Transl. Med. 64:171–77 [Google Scholar]
  51. Kis K, Liu X, Hagood JS. 51.  2011. Myofibroblast differentiation and survival in fibrotic disease. Expert Rev. Mol. Med. 13:e27 [Google Scholar]
  52. Ferrer RA, Saalbach A, Gränwedel M, Lohmann N, Forstreuter I. 52.  et al. 2017. Dermal fibroblasts promote alternative macrophage activation improving impaired wound healing. J. Investig. Dermatol. 137:941–50 [Google Scholar]
  53. Ogawa R.53.  2011. Mechanobiology of scarring. Wound Repair. Regen. 19:Suppl. 1s2–9 [Google Scholar]
  54. Rief M, Gautel M, Oesterhelt F, Fernandez JM, Gaub HE. 54.  1997. Reversible unfolding of individual titin immunoglobulin domains by AFM. Science 276:1109–12 [Google Scholar]
  55. Kellermayer MS, Smith SB, Granzier HL, Bustamante C. 55.  1997. Folding-unfolding transitions in single titin molecules characterized with laser tweezers. Science 276:1112–16 [Google Scholar]
  56. Soteriou A, Clarke A, Martin S, Trinick J. 56.  1993. Titin folding energy and elasticity. Proc. R. Soc. B 254:83–6 [Google Scholar]
  57. Erickson HP.57.  1994. Reversible unfolding of fibronectin type III and immunoglobulin domains provides the structural basis for stretch and elasticity of titin and fibronectin. PNAS 91:10114–18 [Google Scholar]
  58. Lu H, Isralewitz B, Krammer A, Vogel V, Schulten K. 58.  1998. Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation. Biophys. J. 75:662–71 [Google Scholar]
  59. Rief M, Gautel M, Schemmel A, Gaub HE. 59.  1998. The mechanical stability of immunoglobulin and fibronectin III domains in the muscle protein titin measured by atomic force microscopy. Biophys. J. 75:3008–14 [Google Scholar]
  60. Gao M, Lu H, Schulten K. 60.  2002. Unfolding of titin domains studied by molecular dynamics simulations. J. Muscle Res. Cell Motil. 23:513–21 [Google Scholar]
  61. Oberhauser AF, Badilla-Fernandez C, Carrion-Vazquez M, Fernandez JM. 61.  2002. The mechanical hierarchies of fibronectin observed with single-molecule AFM. J. Mol. Biol. 319:433–47 [Google Scholar]
  62. Craig D, Gao M, Schulten K, Vogel V. 62.  2004. Tuning the mechanical stability of fibronectin type III modules through sequence variations. Structure 12:21–30 [Google Scholar]
  63. Krammer A, Lu H, Isralewitz B, Schulten K, Vogel V. 63.  1999. Forced unfolding of the fibronectin type III module reveals a tensile molecular recognition switch. PNAS 96:1351–56 [Google Scholar]
  64. Marszalek PE, Lu H, Li H, Carrion-Vazquez M, Oberhauser AF. 64.  et al. 1999. Mechanical unfolding intermediates in titin modules. Nature 402:100–3 [Google Scholar]
  65. Rief M, Grubmüller H. 65.  2002. Force spectroscopy of single biomolecules. ChemPhysChem 3:255–61 [Google Scholar]
  66. Martino MM, Hubbell JA. 66.  2010. The 12th–14th type III repeats of fibronectin function as a highly promiscuous growth factor-binding domain. FASEB J 24:4711–21 [Google Scholar]
  67. Sarrazy V, Koehler A, Chow ML, Zimina E, Li CX. 67.  et al. 2014. Integrins αvβ5 and αvβ3 promote latent TGF-β1 activation by human cardiac fibroblast contraction. Cardiovasc. Res. 102:407–17 [Google Scholar]
  68. Wan AM, Chandler EM, Madhavan M, Infanger DW, Ober CK. 68.  et al. 2013. Fibronectin conformation regulates the proangiogenic capability of tumor-associated adipogenic stromal cells. Biochim. Biophys. Acta 1830:4314–20 [Google Scholar]
  69. Sack KD, Teran M, Nugent MA. 69.  2016. Extracellular matrix stiffness controls VEGF signaling and processing in endothelial cells. J. Cell Physiol. 231:2026–39 [Google Scholar]
  70. Alon R, Cahalon L, Hershkoviz R, Elbaz D, Reizis B. 70.  et al. 1994. TNF-α binds to the N-terminal domain of fibronectin and augments the β1-integrin-mediated adhesion of CD4+ T lymphocytes to the glycoprotein. J. Immunol. 152:1304–13 [Google Scholar]
  71. Tavian D, De Petro G, Colombi M, Portolani N, Giulini SM. 71.  et al. 1994. RT-PCR detection of fibronectin EDA+ and EDB+ mRNA isoforms: molecular markers for hepatocellular carcinoma. Int. J. Cancer 56:820–5 [Google Scholar]
  72. Shinde AV, Bystroff C, Wang C, Vogelezang MG, Vincent PA. 72.  et al. 2008. Identification of the peptide sequences within the EIIIA (EDA) segment of fibronectin that mediate integrin α9β1-dependent cellular activities. J. Biol. Chem. 283:2858–70 [Google Scholar]
  73. Sun X, Fa P, Cui Z, Xia Y, Sun L. 73.  et al. 2014. The EDA-containing cellular fibronectin induces epithelial-mesenchymal transition in lung cancer cells through integrin α9β1-mediated activation of PI3-K/AKT and Erk1/2. Carcinogenesis 35:184–91 [Google Scholar]
  74. Manabe R, Oh-e N, Sekiguchi K. 74.  1999. Alternatively spliced EDA segment regulates fibronectin-dependent cell cycle progression and mitogenic signal transduction. J. Biol. Chem. 274:5919–24 [Google Scholar]
  75. Pupek M, Jasonek J, Katnik-Prastowska I. 75.  2013. EDA-containing fibronectin levels in the cerebrospinal fluid of children with meningitis. Ann. Clin. Lab. Sci. 43:257–66 [Google Scholar]
  76. Dietrich T, Berndorff D, Heinrich T, Hucko T, Stepina E. 76.  et al. 2015. Targeted ED-B fibronectin SPECT in vivo imaging in experimental atherosclerosis. Q. J. Nucl. Med. Mol. Imaging 59:228–37 [Google Scholar]
  77. Lv WQ, Peng J, Wang HC, Chen DP, Yang Y. 77.  et al. 2017. Expression of cancer cell-derived IgG and extra domain A-containing fibronectin in salivary adenoid cystic carcinoma. Arch. Oral Biol. 81:15–20 [Google Scholar]
  78. Grinnell F, Zhu M. 78.  1996. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, α1-proteinase inhibitor, and α2-macroglobulin. J. Investig. Dermatol. 106:335–41 [Google Scholar]
  79. Zhang X, Chen CT, Bhargava M, Torzilli PA. 79.  2012. A comparative study of fibronectin cleavage by MMP-1, -3, -13, and -14. Cartilage 3:267–77 [Google Scholar]
  80. Modol T, Brice N, Ruiz de Galarreta M, Garcia Garzon A, Iraburu MJ. 80.  et al. 2014. Fibronectin peptides as potential regulators of hepatic fibrosis through apoptosis of hepatic stellate cells. J. Cell. Physiol. 230:546–53 [Google Scholar]
  81. Morla A, Zhang Z, Ruoslahti E. 81.  1994. Superfibronectin is a functionally distinct form of fibronectin. Nature 367:193–96 [Google Scholar]
  82. Julier Z, Martino MM, de Titta A, Jeanbart L, Hubbell JA. 82.  2015. The TLR4 agonist fibronectin extra domain A is cryptic, exposed by elastase-2; use in a fibrin matrix cancer vaccine. Sci. Rep. 5:8569 [Google Scholar]
  83. Krammer A, Craig D, Thomas WE, Schulten K, Vogel V. 83.  2002. A structural model for force regulated integrin binding to fibronectin's RGD-synergy site. Matrix Biol 21:139–47 [Google Scholar]
  84. Altroff H, Schlinkert R, van der Walle CF, Bernini A, Campbell ID. 84.  et al. 2004. Interdomain tilt angle determines integrin-dependent function of the ninth and tenth FIII domains of human fibronectin. J. Biol. Chem. 279:55995–6003 [Google Scholar]
  85. Hubbard B, Buczek-Thomas JA, Nugent MA, Smith ML. 85.  2016. Fibronectin fiber extension decreases cell spreading and migration. J. Cell. Physiol. 231:1728–36 [Google Scholar]
  86. Cao L, Nicosia J, Larouche J, Zhang Y, Bachman H. 86.  et al. 2017. Detection of an integrin-binding mechanoswitch within fibronectin during tissue formation and fibrosis. ACS Nano 11:77110–17 [Google Scholar]
  87. Pankov R, Yamada KM. 87.  2002. Fibronectin at a glance. J. Cell Sci. 115:Pt. 203861–63 [Google Scholar]
  88. Katz BZ, Zamir E, Bershadsky A, Kam Z, Yamada KM, Geiger B. 88.  2000. Physical state of the extracellular matrix regulates the structure and molecular composition of cell-matrix adhesions. Mol. Biol. Cell 11:1047–60 [Google Scholar]
  89. Balaban NQ, Schwarz US, Riveline D, Goichberg P, Tzur G. 89.  et al. 2001. Force and focal adhesion assembly: a close relationship studied using elastic micropatterned substrates. Nat. Cell Biol. 3:466–72 [Google Scholar]
  90. Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T. 90.  et al. 2001. Focal contacts as mechanosensors. J. Cell Biol. 153:1175–86 [Google Scholar]
  91. Baneyx G, Baugh L, Vogel V. 91.  2001. Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer. PNAS 98:14464–68 [Google Scholar]
  92. Smith ML, Gourdon D, Little WC, Kubow KE, Eguiluz RA. 92.  et al. 2007. Force-induced unfolding of fibronectin in the extracellular matrix of living cells. PLOS Biol 5:e268 [Google Scholar]
  93. Mosher DF, Johnson RB. 93.  1983. In vitro formation of disulfide-bonded fibronectin multimers. J. Biol. Chem. 258:6595–601 [Google Scholar]
  94. Wolff C, Lai CS. 94.  1990. Inter-sulfhydryl distances in plasma fibronectin determined by fluorescence energy transfer: effect of environmental factors. Biochemistry 29:3354–61 [Google Scholar]
  95. Baneyx G, Baugh L, Vogel V. 95.  2002. Fibronectin extension and unfolding within cell matrix fibrils controlled by cytoskeletal tension. PNAS 99:5139–43 [Google Scholar]
  96. Sawada Y, Sheetz MP. 96.  2002. Force transduction by Triton cytoskeletons. J. Cell Biol. 156:609–15 [Google Scholar]
  97. Vogel V, Sheetz M. 97.  2006. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7:265–75 [Google Scholar]
  98. Johnson CP, Tang HY, Carag C, Speicher DW, Discher DE. 98.  2007. Forced unfolding of proteins within cells. Science 317:663–66 [Google Scholar]
  99. Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M. 99.  et al. 2010. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466:263–66 [Google Scholar]
  100. Wang X, Ha T. 100.  2013. Defining single molecular forces required to activate integrin and notch signaling. Science 340:991–94 [Google Scholar]
  101. Meng F, Suchyna TM, Lazakovitch E, Gronostajski RM, Sachs F. 101.  2011. Real time FRET based detection of mechanical stress in cytoskeletal and extracellular matrix proteins. Cell. Mol. Bioeng. 4:148–59 [Google Scholar]
  102. Seong J, Ouyang M, Kim T, Sun J, Wen PC. 102.  et al. 2011. Detection of focal adhesion kinase activation at membrane microdomains by fluorescence resonance energy transfer. Nat. Commun. 2:406 [Google Scholar]
  103. Guo J, Sachs F, Meng F. 103.  2014. Fluorescence-based force/tension sensors: a novel tool to visualize mechanical forces in structural proteins in live cells. Antioxid. Redox Signal. 20:986–99 [Google Scholar]
  104. Jurchenko C, Salaita KS. 104.  2015. Lighting up the force: investigating mechanisms of mechanotransduction using fluorescent tension probes. Mol. Cell. Biol. 35:2570–82 [Google Scholar]
  105. Yamashita S, Tsuboi T, Ishinabe N, Kitaguchi T, Michiue T. 105.  2016. Wide and high resolution tension measurement using FRET in embryo. Sci. Rep. 6:28535 [Google Scholar]
  106. Little WC, Schwartlander R, Smith ML, Gourdon D, Vogel V. 106.  2009. Stretched extracellular matrix proteins turn fouling and are functionally rescued by the chaperones albumin and casein. Nano Lett 9:4158–67 [Google Scholar]
  107. Chernousov MA, Faerman AI, Frid MG, Printseva O, Koteliansky VE. 107.  1987. Monoclonal antibody to fibronectin which inhibits extracellular matrix assembly. FEBS Lett 217:124–28 [Google Scholar]
  108. Carnemolla B, Leprini A, Allemanni G, Saginati M, Zardi L. 108.  1992. The inclusion of the type III repeat ED-B in the fibronectin molecule generates conformational modifications that unmask a cryptic sequence. J. Biol. Chem. 267:24689–92 [Google Scholar]
  109. Balza E, Sassi F, Ventura E, Parodi A, Fossati S. 109  et al. 2009. A novel human fibronectin cryptic sequence unmasked by the insertion of the angiogenesis-associated extra type III domain B. Int. J. Cancer 125:751–58 [Google Scholar]
  110. Baneyx G, Vogel V. 110.  1999. Self-assembly of fibronectin into fibrillar networks underneath dipalmitoyl phosphatidylcholine monolayers: role of lipid matrix and tensile forces. PNAS 96:12518–23 [Google Scholar]
  111. Zhang Q, Checovich WJ, Peters DM, Albrecht RM, Mosher DF. 111.  1994. Modulation of cell surface fibronectin assembly sites by lysophosphatidic acid. J. Cell Biol. 127:1447–59 [Google Scholar]
  112. Leiss M, Beckmann K, Giros A, Costell M, Fassler R. 112.  2008. The role of integrin binding sites in fibronectin matrix assembly in vivo. Curr. Opin. Cell Biol. 20:502–7 [Google Scholar]
  113. Hocking DC, Kowalski K. 113.  2002. A cryptic fragment from fibronectin's III1 module localizes to lipid rafts and stimulates cell growth and contractility. J. Cell Biol. 158:175–84 [Google Scholar]
  114. Sechler JL, Rao H, Cumiskey AM, Vega-Colon I, Smith MS. 114.  et al. 2001. A novel fibronectin binding site required for fibronectin fibril growth during matrix assembly. J. Cell Biol. 154:1081–88 [Google Scholar]
  115. Ohashi T, Erickson HP. 115.  2005. Domain unfolding plays a role in superfibronectin formation. J. Biol. Chem. 280:39143–51 [Google Scholar]
  116. Litvinovich SV, Brew SA, Aota S, Akiyama SK, Haudenschild C, Ingham KC. 116.  1998. Formation of amyloid-like fibrils by self-association of a partially unfolded fibronectin type III module. J. Mol. Biol. 280:245–58 [Google Scholar]
  117. Hocking DC, Smith RK, McKeown-Longo PJ. 117.  1996. A novel role for the integrin-binding III-10 module in fibronectin matrix assembly. J. Cell Biol. 133:431–44 [Google Scholar]
  118. Gee EP, Yuksel D, Stultz CM, Ingber DE. 118.  2013. SLLISWD sequence in the 10FNIII domain initiates fibronectin fibrillogenesis. J. Biol. Chem. 288:21329–40 [Google Scholar]
  119. Bultmann H, Santas AJ, Peters DM. 119.  1998. Fibronectin fibrillogenesis involves the heparin II binding domain of fibronectin. J. Biol. Chem. 273:2601–9 [Google Scholar]
  120. Maqueda A, Moyano JV, Hernandez Del Cerro M, Peters DM, Garcia-Pardo A. 120.  2007. The heparin III-binding domain of fibronectin (III4–5 repeats) binds to fibronectin and inhibits fibronectin matrix assembly. Matrix Biol 26:642–51 [Google Scholar]
  121. Gao M, Craig D, Lequin O, Campbell ID, Vogel V, Schulten K. 121.  2003. Structure and functional significance of mechanically unfolded fibronectin type III1 intermediates. PNAS 100:14784–89 [Google Scholar]
  122. Sechler JL, Takada Y, Schwarzbauer JE. 122.  1996. Altered rate of fibronectin matrix assembly by deletion of the first type III repeats. J. Cell Biol. 134:573–83 [Google Scholar]
  123. Früh SM, Schoen I, Ries J, Vogel V. 123.  2015. Molecular architecture of native fibronectin fibrils. Nat. Commun. 6:7275 [Google Scholar]
  124. Briknarova K, Akerman ME, Hoyt DW, Ruoslahti E, Ely KR. 124.  2003. Anastellin, an FN3 fragment with fibronectin polymerization activity, resembles amyloid fibril precursors. J. Mol. Biol. 332:205–15 [Google Scholar]
  125. Ohashi T, Augustus AM, Erickson HP. 125.  2009. Transient opening of fibronectin type III (FNIII) domains: the interaction of the third FNIII domain of FN with anastellin. Biochemistry 48:4189–97 [Google Scholar]
  126. Craig D, Krammer A, Schulten K, Vogel V. 126.  2001. Comparison of the early stages of forced unfolding for fibronectin type III modules. PNAS 98:5590–95 [Google Scholar]
  127. Yi M, Ruoslahti E. 127.  2001. A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis. PNAS 98:620–24 [Google Scholar]
  128. Ambesi A, McKeown-Longo PJ. 128.  2009. Anastellin, the angiostatic fibronectin peptide, is a selective inhibitor of lysophospholipid signaling. Mol. Cancer Res. 7:255–65 [Google Scholar]
  129. Klein RM, Zheng M, Ambesi A, Van De Water L, McKeown-Longo PJ. 129.  2003. Stimulation of extracellular matrix remodeling by the first type III repeat in fibronectin. J. Cell Sci. 116:4663–74 [Google Scholar]
  130. Ambesi A, Klein RM, Pumiglia KM, McKeown-Longo PJ. 130.  2005. Anastellin, a fragment of the first type III repeat of fibronectin, inhibits extracellular signal-regulated kinase and causes G1 arrest in human microvessel endothelial cells. Cancer Res 65:148–56 [Google Scholar]
  131. You R, Klein RM, Zheng M, McKeown-Longo PJ. 131.  2009. Regulation of p38 MAP kinase by anastellin is independent of anastellin's effect on matrix fibronectin. Matrix Biol 28:101–9 [Google Scholar]
  132. Peleg O, Savin T, Kolmakov GV, Salib IG, Balazs AC. 132.  et al. 2012. Fibers with integrated mechanochemical switches: minimalistic design principles derived from fibronectin. Biophys. J. 103:1909–18 [Google Scholar]
  133. Sun BK, Siprashvili Z, Khavari PA. 133.  2014. Advances in skin grafting and treatment of cutaneous wounds. Science 346:941–45 [Google Scholar]
  134. Bryers JD, Giachelli CM, Ratner BD. 134.  2012. Engineering biomaterials to integrate and heal: the biocompatibility paradigm shifts. Biotechnol. Bioeng. 109:1898–911 [Google Scholar]
  135. Kadler KE, Hill A, Canty-Laird EG. 135.  2008. Collagen fibrillogenesis: fibronectin, integrins, and minor collagens as organizers and nucleators. Curr. Opin. Cell Biol. 20:495–501 [Google Scholar]
  136. Sottile J, Shi F, Rublyevska I, Chiang HY, Lust J, Chandler J. 136.  2007. Fibronectin-dependent collagen I deposition modulates the cell response to fibronectin. Am. J. Physiol. Cell Physiol. 293:C1934–46 [Google Scholar]
  137. Rozario T, Dzamba B, Weber GF, Davidson LA, DeSimone DW.137.  2009. The physical state of fibronectin matrix differentially regulates morphogenetic movements in vivo. . Dev. Biol. 327:386–98 [Google Scholar]
  138. Lukjanenko L, Jung MJ, Hegde N, Perruisseau-Carrier C, Migliavacca E. 138.  et al. 2016. Loss of fibronectin from the aged stem cell niche affects the regenerative capacity of skeletal muscle in mice. Nat. Med. 22:897–905 [Google Scholar]
  139. Saeger J, Hytönen VP, Klotzsch E, Vogel V.139.  2012. GFP's mechanical intermediate states. PLOS ONE 7:10e46962 [Google Scholar]
  140. Schwarz-Linek U, Werner JM, Pickford AR, Gurusiddappa S, Kim JH. 140.  et al. 2003. Pathogenic bacteria attach to human fibronectin through a tandem β-zipper. Nature 423:177–81 [Google Scholar]
  141. Schwarz-Linek U, Pilka ES, Pickford AR, Kim JH, Hook M. 141.  et al. 2004. High affinity streptococcal binding to human fibronectin requires specific recognition of sequential F1 modules. J. Biol. Chem. 279:39017–25 [Google Scholar]
  142. Hertig S, Chabria M, Vogel V.142.  2012. Engineering mechanosensitive multivalent receptor-ligand interactions: why the nanolinker regions of bacterial adhesins matter. Nano Lett 12:5162–68 [Google Scholar]
  143. Diao J, Maniotis AJ, Folberg R, Tajkhorshid E.143.  2010. Interplay of mechanical and binding properties of Fibronectin type I. Theor. Chem. Acc 125:397–405 [Google Scholar]
  144. Sarikaya A, Record R, Wu CC, Tullius B, Badylak S, Ladisch M.144.  2002. Antimicrobial activity associated with extracellular matrices. Tissue Eng 8:63–71 [Google Scholar]
  145. Mitsi M, Hong Z, Costello CE, Nugent MA.145.  2006. Heparin-mediated conformational changes in fibronectin expose vascular endothelial growth factor binding sites. Biochemistry 45:10319–28 [Google Scholar]
  146. Hubbard B, Buczek-Thomas JA, Nugent MA, Smith ML.146.  2014. Heparin-dependent regulation of fibronectin matrix conformation. Matrix Biol 34:124–31 [Google Scholar]
  147. Li B, Lin Z, Mitsi M, Zhang Y, Vogel V.147.  2015. Heparin-induced conformational changes of fibronectin within the extracellular matrix promote hMSC osteogenic differentiation. Biomater. Sci. 3:73–84 [Google Scholar]
  148. Smith EM, Mitsi M, Nugent MA, Symes K.148.  2009. PDGF-A interactions with fibronectin reveal a critical role for heparan sulfate in directed cell migration during Xenopus gastrulation. PNAS 106:21683–88 [Google Scholar]
  149. Vogel S, Arnoldini S, Möller S, Schnabelrauch M, Hempel U.149.  2016. Sulfated hyaluronan alters fibronectin matrix assembly and promotes osteogenic differentiation of human bone marrow stromal cells. Sci. Rep. 6:36418 [Google Scholar]
  150. Sieg DJ, Hauck CR, Schlaepfer DD.150.  1999. Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration. J. Cell Sci. 112:Pt. 162677–91 [Google Scholar]
  151. Martino MM, Tortelli F, Mochizuki M, Traub S, Ben-David D. 151.  et al. 2011. Engineering the growth factor microenvironment with fibronectin domains to promote wound and bone tissue healing. Sci. Transl. Med. 3:100ra89 [Google Scholar]
  152. Mitsi M, Schulz MM, Gousopoulos E, Ochsenbein AM, Detmar M, Vogel V. 152.  2015. Walking the line: a fibronectin fiber-guided assay to probe early steps of (lymph)angiogenesis. PLOS ONE 10:e0145210 [Google Scholar]
  153. Leung E, Xue A, Wang Y, Rougerie P, Sharma VP. 153.  et al. 2017. Blood vessel endothelium-directed tumor cell streaming in breast tumors requires the HGF/C-Met signaling pathway. Oncogene 36:2680–92 [Google Scholar]
  154. Garcia AJ, Boettiger D. 154.  1999. Integrin-fibronectin interactions at the cell-material interface: initial integrin binding and signaling. Biomaterials 20:2427–33 [Google Scholar]
  155. Antia M, Baneyx G, Kubow KE, Vogel V. 155.  2008. Fibronectin in aging extracellular matrix fibrils is progressively unfolded by cells and elicits an enhanced rigidity response. Faraday Discuss 139:229–49 [Google Scholar]
  156. Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y. 156.  et al. 2012. Extracellular-matrix tethering regulates stem-cell fate. Nat. Mater. 11:642–49 [Google Scholar]
  157. Li B, Moshfegh C, Lin Z, Albuschies J, Vogel V. 157.  2013. Mesenchymal stem cells exploit extracellular matrix as mechanotransducer. Sci. Rep. 3:2425 [Google Scholar]
  158. You R, Zheng M, McKeown-Longo PJ. 158.  2010. The first type III repeat in fibronectin activates an inflammatory pathway in dermal fibroblasts. J. Biol. Chem. 285:36255–59 [Google Scholar]
  159. Zheng M, Jones DM, Horzempa C, Prasad A, McKeown-Longo PJ. 159.  2011. The first type iii domain of fibronectin is associated with the expression of cytokines within the lung tumor microenvironment. J. Cancer 2:478–83 [Google Scholar]
  160. Rybak JN, Roesli C, Kaspar M, Villa A, Neri D. 160.  2007. The extra-domain A of fibronectin is a vascular marker of solid tumors and metastases. Cancer Res 67:10948–57 [Google Scholar]
  161. Singh P, Reimer CL, Peters JH, Stepp MA, Hynes RO, Van De Water L. 161.  2004. The spatial and temporal expression patterns of integrin α9β1 and one of its ligands, the EIIIA segment of fibronectin, in cutaneous wound healing. J. Investig. Dermatol. 123:1176–81 [Google Scholar]
  162. Dhanesha N, Ahmad A, Prakash P, Doddapattar P, Lentz SR, Chauhan AK. 162.  2015. Genetic ablation of extra domain A of fibronectin in hypercholesterolemic mice improves stroke outcome by reducing thrombo-inflammation. Circulation 132:2237–47 [Google Scholar]
  163. Muro AF, Chauhan AK, Gajovic S, Iaconcig A, Porro F. 163.  et al. 2003. Regulated splicing of the fibronectin EDA exon is essential for proper skin wound healing and normal lifespan. J. Cell Biol. 162:149–60 [Google Scholar]
  164. Phanish MK, Heidebrecht F, Nabi ME, Shah N, Niculescu-Duvaz I, Dockrell ME. 164.  2015. The regulation of TGFβ1 induced fibronectin EDA exon alternative splicing in human renal proximal tubule epithelial cells. J. Cell Physiol. 230:286–95 [Google Scholar]
  165. Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST. 165.  et al. 2001. The extra domain A of fibronectin activates Toll-like receptor 4. J. Biol. Chem. 276:10229–33 [Google Scholar]
  166. Shinde AV, Kelsh R, Peters JH, Sekiguchi K, Van De Water L McKeown-Longo PJ. 166.  2015. The α4β1 integrin and the EDA domain of fibronectin regulate a profibrotic phenotype in dermal fibroblasts. Matrix Biol 41:26–35 [Google Scholar]
  167. Gupta SK, Vlahakis NE. 167.  2010. Integrin α9β1: unique signaling pathways reveal diverse biological roles. Cell Adh. Migr. 4:194–98 [Google Scholar]
  168. Kohan M, Muro AF, White ES, Berkman N. 168.  2010. EDA-containing cellular fibronectin induces fibroblast differentiation through binding to α4β7 integrin receptor and MAPK/Erk 1/2-dependent signaling. FASEB J 24:4503–12 [Google Scholar]
  169. Altevogt P, Hubbe M, Ruppert M, Lohr J, von Hoegen P. 169.  et al. 1995. The alpha 4 integrin chain is a ligand for alpha 4 beta 7 and alpha 4 beta 1. J. Exp. Med. 182:345–55 [Google Scholar]
  170. Hernandez H, Medina-Ortiz WE, Luan T, Clark AF, McDowell CM. 170.  2017. Crosstalk between transforming growth factor beta-2 and Toll-like receptor 4 in the trabecular meshwork. Investig. Ophthalmol. Vis. Sci. 58:1811–23 [Google Scholar]
  171. Lasarte JJ, Casares N, Gorraiz M, Hervas-Stubbs S, Arribillaga L. 171.  et al. 2007. The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J. Immunol. 178:748–56 [Google Scholar]
  172. Doddapattar P, Gandhi C, Prakash P, Dhanesha N, Grumbach IM. 172.  et al. 2015. Fibronectin splicing variants containing extra domain A promote atherosclerosis in mice through Toll-like receptor 4. Arterioscler. Thromb. Vasc. Biol. 35:2391–400 [Google Scholar]
  173. Prakash P, Kulkarni PP, Lentz SR, Chauhan AK. 173.  2015. Cellular fibronectin containing extra domain A promotes arterial thrombosis in mice through platelet Toll-like receptor 4. Blood 125:3164–72 [Google Scholar]
  174. Rudilla F, Fayolle C, Casares N, Durantez M, Arribillaga L. 174.  et al. 2012. Combination of a TLR4 ligand and anaphylatoxin C5a for the induction of antigen-specific cytotoxic T cell responses. Vaccine 30:2848–58 [Google Scholar]
  175. Acharya M, Sokolovska A, Tam JM, Conway KL, Stefani C. 175.  et al. 2016. αv Integrins combine with LC3 and atg5 to regulate Toll-like receptor signalling in B cells. Nat. Commun. 7:10917 [Google Scholar]
  176. Mansilla C, Gorraiz M, Martinez M, Casares N, Arribillaga L. 176.  et al. 2009. Immunization against hepatitis C virus with a fusion protein containing the extra domain A from fibronectin and the hepatitis C virus NS3 protein. J. Hepatol. 51:520–27 [Google Scholar]
  177. Julier Z, de Titta A, Grimm AJ, Simeoni E, Swartz MA, Hubbell JA. 177.  2016. Fibronectin EDA and CpG synergize to enhance antigen-specific Th1 and cytotoxic responses. Vaccine 34:2453–59 [Google Scholar]
  178. Kelsh R, You R, Horzempa C, Zheng M, McKeown-Longo PJ. 178.  2014. Regulation of the innate immune response by fibronectin: synergism between the III-1 and EDA domains. PLOS ONE 9:e102974 [Google Scholar]
  179. Onder L, Narang P, Scandella E, Chai Q, Iolyeva M. 179.  et al. 2012. IL-7-producing stromal cells are critical for lymph node remodeling. Blood 120:4675–83 [Google Scholar]
  180. Ariel A, Hershkoviz R, Cahalon L, Williams DE, Akiyama SK. 180.  et al. 1997. Induction of T cell adhesion to extracellular matrix or endothelial cell ligands by soluble or matrix-bound interleukin-7. Eur. J. Immunol. 27:2562–70 [Google Scholar]
  181. Borghesi LA, Yamashita Y, Kincade PW. 181.  1999. Heparan sulfate proteoglycans mediate interleukin-7-dependent B lymphopoiesis. Blood 93:140–48 [Google Scholar]
  182. Mackall CL, Fry TJ, Gress RE. 182.  2011. Harnessing the biology of IL-7 for therapeutic application. Nat. Rev. Immunol. 11:330–42 [Google Scholar]
  183. Ortiz Franyuti D, Mitsi M, Vogel V. 183.  2017. Mechanical stretching of fibronectin fibers upregulates binding of interleukin-7. Nano Lett In press. https://doi.org/10.1021/acs.nanolett.7b01617 [Crossref] [Google Scholar]
  184. Kitazawa H, Muegge K, Badolato R, Wang JM, Fogler WE. 184.  et al. 1997. IL-7 activates α4β1 integrin in murine thymocytes. J. Immunol. 159:2259–64 [Google Scholar]
  185. Zhang L, Keane MP, Zhu LX, Sharma S, Rozengurt E. 185.  et al. 2004. Interleukin-7 and transforming growth factor-β play counter-regulatory roles in protein kinase C-δ-dependent control of fibroblast collagen synthesis in pulmonary fibrosis. J. Biol. Chem. 279:28315–19 [Google Scholar]
  186. Cukierman E, Pankov R, Stevens DR, Yamada KM. 186.  2001. Taking cell-matrix adhesions to the third dimension. Science 294:1708–12 [Google Scholar]
  187. Kubow KE, Conrad SK, Horwitz AR. 187.  2013. Matrix microarchitecture and myosin II determine adhesion in 3D matrices. Curr. Biol. 23:1607–19 [Google Scholar]
  188. Abraham S, Sheridan SD, Miller B, Rao RR. 188.  2010. Stable propagation of human embryonic and induced pluripotent stem cells on decellularized human substrates. Biotechnol. Prog. 26:1126–34 [Google Scholar]
  189. Flynn LE.189.  2010. The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials 31:4715–24 [Google Scholar]
  190. Yamada KM, Cukierman E. 190.  2007. Modeling tissue morphogenesis and cancer in 3D. Cell 130:601–10 [Google Scholar]
  191. Kubow KE, Klotzsch E, Smith ML, Gourdon D, Little WC, Vogel V. 191.  2009. Crosslinking of cell-derived 3D scaffolds up-regulates the stretching and unfolding of new extracellular matrix assembled by reseeded cells. Integr. Biol. 1:635–48 [Google Scholar]
  192. Badylak S, Arnoczky S, Plouhar P, Haut R, Mendenhall V. 192.  et al. 1999. Naturally occurring extracellular matrix as a scaffold for musculoskeletal repair. Clin. Orthop. Relat. Res. 367:S333–43 [Google Scholar]
  193. Swinehart IT, Badylak SF. 193.  2016. Extracellular matrix bioscaffolds in tissue remodeling and morphogenesis. Dev. Dyn. 245:351–60 [Google Scholar]
  194. Zeng ZZ, Yao H, Staszewski ED, Rockwood KF, Markwart SM. 194.  et al. 2009. α5β1 integrin ligand PHSRN induces invasion and α5 mRNA in endothelial cells to stimulate angiogenesis. Transl. Oncol. 2:18–20 [Google Scholar]
  195. Saldin LT, Cramer MC, Velankar SS, White LJ, Badylak SF. 195.  2017. Extracellular matrix hydrogels from decellularized tissues: structure and function. Acta Biomater 49:1–15 [Google Scholar]
  196. Weber B, Dijkman PE, Scherman J, Sanders B, Emmert MY. 196.  et al. 2013. Off-the-shelf human decellularized tissue-engineered heart valves in a non-human primate model. Biomaterials 34:7269–80 [Google Scholar]
  197. Tukmachev D, Forostyak S, Koci Z, Zaviskova K, Vackova I. 197.  et al. 2016. Injectable extracellular matrix hydrogels as scaffolds for spinal cord injury repair. Tissue Eng. A 22:306–17 [Google Scholar]
  198. Jang J, Kim TG, Kim BS, Kim SW, Kwon SM, Cho DW. 198.  2016. Tailoring mechanical properties of decellularized extracellular matrix bioink by vitamin B2-induced photo-crosslinking. Acta Biomater 33:88–95 [Google Scholar]
  199. Cao L, Zeller MK, Fiore VF, Strane P, Bermudez H, Barker TH. 199.  2012. Phage-based molecular probes that discriminate force-induced structural states of fibronectin in vivo. PNAS 109:7251–56 [Google Scholar]
  200. Gligorijevic B, Bergman A, Condeelis J. 200.  2014. Multiparametric classification links tumor microenvironments with tumor cell phenotype. PLOS Biol 12:e1001995 [Google Scholar]
  201. Ishii G, Ochiai A, Neri S. 201.  2016. Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment. Adv. Drug Deliv. Rev. 99:186–96 [Google Scholar]
  202. Wang K, Andresen Eguiluz RC, Wu F, Seo BR, Fischbach C, Gourdon D. 202.  2015. Stiffening and unfolding of early deposited-fibronectin increase proangiogenic factor secretion by breast cancer-associated stromal cells. Biomaterials 54:63–71 [Google Scholar]
  203. Morris BA, Burkel B, Ponik SM, Fan J, Condeelis JS. 203.  et al. 2016. Collagen matrix density drives the metabolic shift in breast cancer cells. EBioMedicine 13:146–56 [Google Scholar]
  204. Acerbi I, Cassereau L, Dean I, Shi Q, Au A. 204.  et al. 2015. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. 7:1120–34 [Google Scholar]
  205. Legant WR, Chen CS, Vogel V. 205.  2012. Force-induced fibronectin assembly and matrix remodeling in a 3D microtissue model of tissue morphogenesis. Integr. Biol. 4:1164–74 [Google Scholar]
  206. Ruoslahti E.206.  2003. The RGD story: a personal account. Matrix Biol 22:6459–65 [Google Scholar]
  207. Aota S, Nomizu M, Yamada KM. 207.  1994. The short amino acid sequence Pro-His-Ser-Arg-Asn in human fibronectin enhances cell-adhesive function. J. Biol. Chem. 269:4024756–61 [Google Scholar]
  208. Hertig S, Goddard TD, Johnson GT, Ferrin TE. 208.  2015. Multidomain assembler (MDA) generates models of large multidomain proteins. Biophys. J. 108:92097–102 [Google Scholar]
  209. Yalak G, Vogel V. 209.  2015. Ectokinases as novel cancer markers and drug targets in cancer therapy. Cancer Med 4:3404–14 [Google Scholar]
/content/journals/10.1146/annurev-physiol-021317-121312
Loading
/content/journals/10.1146/annurev-physiol-021317-121312
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error