1932

Abstract

In their native environment, cells are immersed in a complex milieu of biochemical and biophysical cues. These cues may include growth factors, the extracellular matrix, cell–cell contacts, stiffness, and topography, and they are responsible for regulating cellular behaviors such as adhesion, proliferation, migration, apoptosis, and differentiation. The decision-making process used to convert these extracellular inputs into actions is highly complex and sensitive to changes both in the type of individual cue (e.g., growth factor dose/level, timing) and in how these individual cues are combined (e.g., homotypic/heterotypic combinations). In this review, we highlight recent advances in the development of engineering-based approaches to study the cellular decision-making process. Specifically, we discuss the use of biomaterial platforms that enable controlled and tailored delivery of individual and combined cues, as well as the application of computational modeling to analyses of the complex cellular decision-making networks.

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2018-06-04
2024-04-20
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Literature Cited

  1. 1.  Downward J 2001. The ins and outs of signalling. Nature 411:759–62
    [Google Scholar]
  2. 2.  Clarke DC, Brown ML, Erickson RA, Shi Y, Liu X 2009. Transforming growth factor β depletion is the primary determinant of Smad signaling kinetics. Mol. Cell. Biol. 29:2443–55
    [Google Scholar]
  3. 3.  Tian D, Kreeger PK 2014. Analysis of the quantitative balance between insulin-like growth factor (IGF)-1 ligand, receptor, and binding protein levels to predict cell sensitivity and therapeutic efficacy. BMC Syst. Biol. 8:98
    [Google Scholar]
  4. 4.  Reddy CC, Wells A, Lauffenburger DA 1996. Receptor-mediated effects on ligand availability influence relative mitogenic potencies of epidermal growth factor and transforming growth factor alpha. J. Cell Physiol. 166:512–22
    [Google Scholar]
  5. 5.  Chang SL, Cavnar SP, Takayama S, Luker GD, Linderman JJ 2015. Cell, isoform, and environment factors shape gradients and modulate chemotaxis. PLOS ONE 10:e0123450
    [Google Scholar]
  6. 6.  Lee RE, Qasaimeh MA, Xia X, Juncker D, Gaudet S 2016. NF-κB signalling and cell fate decisions in response to a short pulse of tumour necrosis factor. Sci. Rep. 6:39519
    [Google Scholar]
  7. 7.  Zi Z, Feng Z, Chapnick DA, Dahl M, Deng D et al. 2011. Quantitative analysis of transient and sustained transforming growth factor β signaling dynamics. Mol. Syst. Biol. 7:492
    [Google Scholar]
  8. 8.  Dinbergs ID, Brown L, Edelman ER 1996. Cellular response to transforming growth factor–β1 and basic fibroblast growth factor depends on release kinetics and extracellular matrix interactions. J. Biol. Chem. 271:29822–29
    [Google Scholar]
  9. 9.  Kuhl PR, Griffith-Cima LG 1996. Tethered epidermal growth factor as a paradigm for growth factor–induced stimulation from the solid phase. Nat. Med. 2:1022–27
    [Google Scholar]
  10. 10.  Fan VH, Tamama K, Au A, Littrell R, Richardson LB et al. 2007. Tethered epidermal growth factor provides a survival advantage to mesenchymal stem cells. Stem Cells 25:1241–51
    [Google Scholar]
  11. 11.  Rodrigues M, Blair H, Stockdale L, Griffith L, Wells A 2013. Surface tethered epidermal growth factor protects proliferating and differentiating multipotential stromal cells from FasL-induced apoptosis. Stem Cells 31:104–16
    [Google Scholar]
  12. 12.  Nuschke A, Rodrigues M, Rivera J, Yates C, Whaley D et al. 2016. Epidermal growth factor tethered to β-tricalcium phosphate bone scaffolds via a high-affinity binding peptide enhances survival of human mesenchymal stem cells/multipotent stromal cells in an immune-competent parafascial implantation assay in mice. Stem Cells Transl. Med. 5:1580–86
    [Google Scholar]
  13. 13.  McCall JD, Anseth KS 2012. Thiol–ene photopolymerizations provide a facile method to encapsulate proteins and maintain their bioactivity. Biomacromolecules 13:2410–17
    [Google Scholar]
  14. 14.  Anderson SM, Chen TT, Iruela-Arispe ML, Segura T 2009. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2) by engineered surfaces with electrostatically or covalently immobilized VEGF. Biomaterials 30:4618–28
    [Google Scholar]
  15. 15.  Kim CS, Mitchell IP, Desotell AW, Kreeger PK, Masters KS 2016. Immobilized epidermal growth factor stimulates persistent, directed keratinocyte migration via activation of PLCγ1. FASEB J 30:2580–90
    [Google Scholar]
  16. 16.  Anderson SM, Shergill B, Barry ZT, Manousiouthakis E, Chen TT et al. 2011. VEGF internalization is not required for VEGFR-2 phosphorylation in bioengineered surfaces with covalently linked VEGF. Integr. Biol. 3:887–96
    [Google Scholar]
  17. 17.  Puccinelli TJ, Bertics PJ, Masters KS 2010. Regulation of keratinocyte signaling and function via changes in epidermal growth factor presentation. Acta Biomater 6:3415–25
    [Google Scholar]
  18. 18.  Discher DE, Mooney DJ, Zandstra PW 2009. Growth factors, matrices, and forces combine and control stem cells. Science 324:1673–77
    [Google Scholar]
  19. 19.  Mente PL, Lewis JL 1994. Elastic modulus of calcified cartilage is an order of magnitude less than that of subchondral bone. J. Orthop. Res. 12:637–47
    [Google Scholar]
  20. 20.  Pelham RJ, Wang Y 1997. Cell locomotion and focal adhesions are regulated by substrate flexibility. PNAS 94:13661–65
    [Google Scholar]
  21. 21.  Yeung T, Georges PC, Flanagan LA, Marg B, Ortiz M et al. 2005. Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion. Cell Motil. Cytoskelet. 60:24–34
    [Google Scholar]
  22. 22.  Engler AJ, Sen S, Sweeney HL, Discher DE 2006. Matrix elasticity directs stem cell lineage specification. Cell 126:677–89
    [Google Scholar]
  23. 23.  Trappmann B, Gautrot JE, Connelly JT, Strange DG, Li Y et al. 2012. Extracellular-matrix tethering regulates stem-cell fate. Nat. Mater. 11:642–49
    [Google Scholar]
  24. 24.  Wen JH, Vincent LG, Fuhrmann A, Choi YS, Hribar KC et al. 2014. Interplay of matrix stiffness and protein tethering in stem cell differentiation. Nat. Mater. 13:979–87
    [Google Scholar]
  25. 25.  Caliari SR, Vega SL, Kwon M, Soulas EM, Burdick JA 2016. Dimensionality and spreading influence MSC YAP/TAZ signaling in hydrogel environments. Biomaterials 103:314–23
    [Google Scholar]
  26. 26.  Notbohm J, Lesman A, Rosakis P, Tirrell DA, Ravichandran G 2015. Microbuckling of fibrin provides a mechanism for cell mechanosensing. J. R. Soc. Interface 12:20150320
    [Google Scholar]
  27. 27.  Baker BM, Trappmann B, Wang WY, Sakar MS, Kim IL et al. 2015. Cell-mediated fibre recruitment drives extracellular matrix mechanosensing in engineered fibrillar microenvironments. Nat. Mater. 14:1262–68
    [Google Scholar]
  28. 28.  Bonnans C, Chou J, Werb Z 2014. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15:786–801
    [Google Scholar]
  29. 29.  Guvendiren M, Burdick JA 2012. Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics. Nat. Commun. 3:792
    [Google Scholar]
  30. 30.  Mabry KM, Lawrence RL, Anseth KS 2015. Dynamic stiffening of poly(ethylene glycol)-based hydrogels to direct valvular interstitial cell phenotype in a three-dimensional environment. Biomaterials 49:47–56
    [Google Scholar]
  31. 31.  Kirschner CM, Alge DL, Gould ST, Anseth KS 2014. Clickable, photodegradable hydrogels to dynamically modulate valvular interstitial cell phenotype. Adv. Healthc. Mater. 3:649–57
    [Google Scholar]
  32. 32.  Stowers RS, Allen SC, Suggs LJ 2015. Dynamic phototuning of 3D hydrogel stiffness. PNAS 112:1953–58
    [Google Scholar]
  33. 33.  Rosales AM, Mabry KM, Nehls EM, Anseth KS 2015. Photoresponsive elastic properties of azobenzene-containing poly(ethylene-glycol)-based hydrogels. Biomacromolecules 16:798–806
    [Google Scholar]
  34. 34.  Gasiorowski JZ, Murphy CJ, Nealey PF 2013. Biophysical cues and cell behavior: the big impact of little things. Annu. Rev. Biomed. Eng. 15:155–76
    [Google Scholar]
  35. 35.  Guvendiren M, Burdick JA 2013. Stem cell response to spatially and temporally displayed and reversible surface topography. Adv. Healthc. Mater. 2:155–64
    [Google Scholar]
  36. 36.  Mascharak S, Benitez PL, Proctor AC, Madl CM, Hu KH et al. 2017. YAP-dependent mechanotransduction is required for proliferation and migration on native-like substrate topography. Biomaterials 115:155–66
    [Google Scholar]
  37. 37.  Hutson HN, Marohl T, Anderson M, Eliceiri K, Campagnola P, Masters KS 2016. Calcific aortic valve disease is associated with layer-specific alterations in collagen architecture. PLOS ONE 11:e0163858
    [Google Scholar]
  38. 38.  Wen B, Campbell KR, Tilbury K, Nadiarnykh O, Brewer MA et al. 2016. 3D texture analysis for classification of second harmonic generation images of human ovarian cancer. Sci. Rep. 6:35734
    [Google Scholar]
  39. 39.  Gao L, Kupfer ME, Jung JP, Yang L, Zhang P et al. 2017. Myocardial tissue engineering with cells derived from human-induced pluripotent stem cells and a native-like, high-resolution, 3-dimensionally printed scaffold. Circ. Res. 120:1318–25
    [Google Scholar]
  40. 40.  Provenzano PP, Eliceiri KW, Campbell JM, Inman DR, White JG, Keely PJ 2006. Collagen reorganization at the tumor–stromal interface facilitates local invasion. BMC Med 4:38
    [Google Scholar]
  41. 41.  Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW et al. 2011. Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am. J. Pathol. 178:1221–32
    [Google Scholar]
  42. 42.  Carey SP, Goldblatt ZE, Martin KE, Romero B, Williams RM, Reinhart-King CA 2016. Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK. Integr. Biol. 8:821–35
    [Google Scholar]
  43. 43.  Culver JC, Hoffmann JC, Poche RA, Slater JH, West JL, Dickinson ME 2012. Three-dimensional biomimetic patterning in hydrogels to guide cellular organization. Adv. Mater. 24:2344–48
    [Google Scholar]
  44. 44.  Brucher BL, Jamall IS 2014. Cell–cell communication in the tumor microenvironment, carcinogenesis, and anticancer treatment. Cell Physiol. Biochem. 34:213–43
    [Google Scholar]
  45. 45.  Kim JH, Kushiro K, Graham NA, Asthagiri AR 2009. Tunable interplay between epidermal growth factor and cell–cell contact governs the spatial dynamics of epithelial growth. PNAS 106:11149–53
    [Google Scholar]
  46. 46.  De Wever O, Hendrix A, De Boeck A, Eertmans F, Westbroek W et al. 2014. Single cell and spheroid collagen type I invasion assay. Methods Mol. Biol. 1070:13–35
    [Google Scholar]
  47. 47.  Mrksich M, Dike LE, Tien J, Ingber DE, Whitesides GM 1997. 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. 235:305–13
    [Google Scholar]
  48. 48.  Li CY, Stevens KR, Schwartz RE, Alejandro BS, Huang JH, Bhatia SN 2014. Micropatterned cell–cell interactions enable functional encapsulation of primary hepatocytes in hydrogel microtissues. Tissue Eng. A 20:2200–12
    [Google Scholar]
  49. 49.  Pasquale EB 2008. Eph–ephrin bidirectional signaling in physiology and disease. Cell 133:38–52
    [Google Scholar]
  50. 50.  Moon JJ, Lee SH, West JL 2007. Synthetic biomimetic hydrogels incorporated with ephrin-A1 for therapeutic angiogenesis. Biomacromolecules 8:42–49
    [Google Scholar]
  51. 51.  Lin CC, Anseth KS 2011. Cell-cell communication mimicry with poly(ethylene glycol) hydrogels for enhancing β-cell function. PNAS 108:6380–85
    [Google Scholar]
  52. 52.  Bray SJ 2006. Notch signalling: A simple pathway becomes complex. Nat. Rev. Mol. Cell Biol. 7:678–89
    [Google Scholar]
  53. 53.  Tung JC, Paige SL, Ratner BD, Murry CE, Giachelli CM 2014. Engineered biomaterials control differentiation and proliferation of human-embryonic-stem-cell-derived cardiomyocytes via timed Notch activation. Stem Cell Rep 2:271–81
    [Google Scholar]
  54. 54.  Toth B, Ben-Moshe S, Gavish A, Barkai N, Itzkovitz S 2017. Early commitment and robust differentiation in colonic crypts. Mol. Syst. Biol. 13:902
    [Google Scholar]
  55. 55.  Nardini JT, Chapnick DA, Liu X, Bortz DM 2016. Modeling keratinocyte wound healing dynamics: Cell–cell adhesion promotes sustained collective migration. J. Theor. Biol. 400:103–17
    [Google Scholar]
  56. 56.  Bian L, Guvendiren M, Mauck RL, Burdick JA 2013. Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis. PNAS 110:10117–22
    [Google Scholar]
  57. 57.  Vega SL, Kwon M, Mauck RL, Burdick JA 2016. Single cell imaging to probe mesenchymal stem cell N-cadherin mediated signaling within hydrogels. Ann. Biomed. Eng. 44:1921–30
    [Google Scholar]
  58. 58.  Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J 2000. Vascular-specific growth factors and blood vessel formation. Nature 407:242–48
    [Google Scholar]
  59. 59.  Chen RR, Silva EA, Yuen WW, Mooney DJ 2007. Spatio-temporal VEGF and PDGF delivery patterns blood vessel formation and maturation. Pharm. Res. 24:258–64
    [Google Scholar]
  60. 60.  Hao X, Silva EA, Månsson-Broberg A, Grinnemo K-H, Siddiqui AJ et al. 2007. Angiogenic effects of sequential release of VEGF-A165 and PDGF-BB with alginate hydrogels after myocardial infarction. Cardiovasc. Res. 75:178–85
    [Google Scholar]
  61. 61.  Vo TN, Kasper FK, Mikos AG 2012. Strategies for controlled delivery of growth factors and cells for bone regeneration. Adv. Drug Deliv. Rev. 64:1292–309
    [Google Scholar]
  62. 62.  Martino MM, Brkic S, Bovo E, Burger M, Schaefer DJ et al. 2015. Extracellular matrix and growth factor engineering for controlled angiogenesis in regenerative medicine. Front. Bioeng. Biotechnol. 3:45
    [Google Scholar]
  63. 63.  Willerth SM 2017. Biomimetic strategies for replicating the neural stem cell niche. Curr. Opin. Chem. Eng. 15:8–14
    [Google Scholar]
  64. 64.  Lee K, Silva EA, Mooney DJ 2011. Growth factor delivery–based tissue engineering: general approaches and a review of recent developments. J. R. Soc. Interface 8:153–70
    [Google Scholar]
  65. 65.  Janes KA, Albeck JG, Gaudet S, Sorger PK, Lauffenburger DA, Yaffe MB 2005. A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis. Science 310:1646
    [Google Scholar]
  66. 66.  Walters BD, Stegemann JP 2014. Strategies for directing the structure and function of three-dimensional collagen biomaterials across length scales. Acta Biomater 10:1488–501
    [Google Scholar]
  67. 67.  Regier MC, Montanez-Sauri SI, Schwartz MP, Murphy WL, Beebe DJ, Sung KE 2017. The influence of biomaterials on cytokine production in 3D cultures. Biomacromolecules 18:709–18
    [Google Scholar]
  68. 68.  Flaim CJ, Chien S, Bhatia SN 2005. An extracellular matrix microarray for probing cellular differentiation. Nat. Methods 2:119–25
    [Google Scholar]
  69. 69.  Kaylan KB, Ermilova V, Yada RC, Underhill GH 2016. Combinatorial microenvironmental regulation of liver progenitor differentiation by Notch ligands, TGFβ, and extracellular matrix. Sci. Rep. 6:23490
    [Google Scholar]
  70. 70.  Carrion B, Souzanchi MF, Wang VT, Tiruchinapally G, Shikanov A et al. 2016. The synergistic effects of matrix stiffness and composition on the response of chondroprogenitor cells in a 3D precondensation microenvironment. Adv. Healthc. Mater. 5:1192–202
    [Google Scholar]
  71. 71.  Rahmany MB, Van Dyke M 2013. Biomimetic approaches to modulate cellular adhesion in biomaterials: a review. Acta Biomater 9:5431–37
    [Google Scholar]
  72. 72.  Benoit DS, Anseth KS 2005. The effect on osteoblast function of colocalized RGD and PHSRN epitopes on PEG surfaces. Biomaterials 26:5209–20
    [Google Scholar]
  73. 73.  Ochsenhirt SE, Kokkoli E, McCarthy JB, Tirrell M 2006. Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement. Biomaterials 27:3863–74
    [Google Scholar]
  74. 74.  Jung JP, Moyano JV, Collier JH 2011. Multifactorial optimization of endothelial cell growth using modular synthetic extracellular matrices. Integr. Biol. 3:185–96
    [Google Scholar]
  75. 75.  Chen C, Xie J, Deng L, Yang L 2014. Substrate stiffness together with soluble factors affects chondrocyte mechanoresponses. ACS Appl. Mater. Interfaces 6:16106–16
    [Google Scholar]
  76. 76.  Allen JL, Cooke ME, Alliston T 2012. ECM stiffness primes the TGFβ pathway to promote chondrocyte differentiation. Mol. Biol. Cell 23:3731–42
    [Google Scholar]
  77. 77.  Banks JM, Mozdzen LC, Harley BA, Bailey RC 2014. The combined effects of matrix stiffness and growth factor immobilization on the bioactivity and differentiation capabilities of adipose-derived stem cells. Biomaterials 35:8951–59
    [Google Scholar]
  78. 78.  Park JS, Chu JS, Tsou AD, Diop R, Tang Z et al. 2011. The effect of matrix stiffness on the differentiation of mesenchymal stem cells in response to TGF-β. Biomaterials 32:3921–30
    [Google Scholar]
  79. 79.  Wickert LE, Pomerenke S, Mitchell I, Masters KS, Kreeger PK 2016. Hierarchy of cellular decisions in collective behavior: implications for wound healing. Sci. Rep. 6:20139
    [Google Scholar]
  80. 80.  Kim J-H, Asthagiri AR 2011. Matrix stiffening sensitizes epithelial cells to EGF and enables the loss of contact inhibition of proliferation. J. Cell Sci. 124:1280
    [Google Scholar]
  81. 81.  Floren M, Bonani W, Dharmarajan A, Motta A, Migliaresi C, Tan W 2016. Human mesenchymal stem cells cultured on silk hydrogels with variable stiffness and growth factor differentiate into mature smooth muscle cell phenotype. Acta Biomater 31:156–66
    [Google Scholar]
  82. 82.  Tan S, Fang JY, Yang Z, Nimni ME, Han B 2014. The synergetic effect of hydrogel stiffness and growth factor on osteogenic differentiation. Biomaterials 35:5294–306
    [Google Scholar]
  83. 83.  Chang FC, Tsao CT, Lin A, Zhang M, Levengood SL, Zhang M 2016. PEG–chitosan hydrogel with tunable stiffness for study of drug response of breast cancer cells. Polymers 8:112
    [Google Scholar]
  84. 84.  Tokuda EY, Leight JL, Anseth KS 2014. Modulation of matrix elasticity with PEG hydrogels to study melanoma drug responsiveness. Biomaterials 35:4310–18
    [Google Scholar]
  85. 85.  Gobaa S, Hoehnel S, Lutolf MP 2015. Substrate elasticity modulates the responsiveness of mesenchymal stem cells to commitment cues. Integr. Biol. 7:1135–42
    [Google Scholar]
  86. 86.  Hansen TD, Koepsel JT, Le NN, Nguyen EH, Zorn S et al. 2014. Biomaterial arrays with defined adhesion ligand densities and matrix stiffness identify distinct phenotypes for tumorigenic and nontumorigenic human mesenchymal cell types. Biomater. Sci. 2:745–56
    [Google Scholar]
  87. 87.  Barcus CE, Keely PJ, Eliceiri KW, Schuler LA 2016. Prolactin signaling through focal adhesion complexes is amplified by stiff extracellular matrices in breast cancer cells. Oncotarget 7:48093–106
    [Google Scholar]
  88. 88.  Kumar S, Weaver VM 2009. Mechanics, malignancy, and metastasis: the force journey of a tumor cell. Cancer Metastasis Rev 28:113–27
    [Google Scholar]
  89. 89.  Zustiak S, Nossal R, Sackett DL 2014. Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs. Biotechnol. Bioeng. 111:396–403
    [Google Scholar]
  90. 90.  Schrader J, Gordon-Walker TT, Aucott RL, van Deemter M, Quaas A et al. 2011. Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells. Hepatology 53:1192–205
    [Google Scholar]
  91. 91.  Wozniak MA, Desai R, Solski PA, Der CJ, Keely PJ 2003. ROCK-generated contractility regulates breast epithelial cell differentiation in response to the physical properties of a three-dimensional collagen matrix. J. Cell Biol. 163:583–95
    [Google Scholar]
  92. 92.  Barcus CE, Keely PJ, Eliceiri KW, Schuler LA 2013. Stiff collagen matrices increase tumorigenic prolactin signaling in breast cancer cells. J. Biol. Chem. 288:12722–32
    [Google Scholar]
  93. 93.  Willits RK, Skornia SL 2004. Effect of collagen gel stiffness on neurite extension. J. Biomater. Sci. Polym. Ed. 15:1521–31
    [Google Scholar]
  94. 94.  Lu P, Weaver VM, Werb Z 2012. The extracellular matrix: a dynamic niche in cancer progression. J. Cell Biol. 196:395–406
    [Google Scholar]
  95. 95.  Wells RG 2013. Tissue mechanics and fibrosis. Biochim. Biophys. Acta 1832:884–90
    [Google Scholar]
  96. 96.  Zhu J 2010. Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering. Biomaterials 31:4639–56
    [Google Scholar]
  97. 97.  Lee KY, Mooney DJ 2012. Alginate: properties and biomedical applications. Prog. Polym. Sci. 37:106–26
    [Google Scholar]
  98. 98.  Nii M, Lai JH, Keeney M, Han LH, Behn A et al. 2013. The effects of interactive mechanical and biochemical niche signaling on osteogenic differentiation of adipose-derived stem cells using combinatorial hydrogels. Acta Biomater 9:5475–83
    [Google Scholar]
  99. 99.  Chaudhuri O, Koshy ST, Branco da Cunha C, Shin JW, Verbeke CS 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]
  100. 100.  Hwang NS, Varghese S, Li H, Elisseeff J 2011. Regulation of osteogenic and chondrogenic differentiation of mesenchymal stem cells in PEG-ECM hydrogels. Cell Tissue Res 344:499–509
    [Google Scholar]
  101. 101.  Jung JP, Sprangers AJ, Byce JR, Su J, Squirrell JM et al. 2013. ECM-incorporated hydrogels cross-linked via native chemical ligation to engineer stem cell microenvironments. Biomacromolecules 14:3102–11
    [Google Scholar]
  102. 102.  Berger AJ, Linsmeier KM, Kreeger PK, Masters KS 2017. Decoupling the effects of stiffness and fiber density on cellular behaviors via an interpenetrating network of gelatin-methacrylate and collagen. Biomaterials 141:125–35
    [Google Scholar]
  103. 103.  Hutson CB, Nichol JW, Aubin H, Bae H, Yamanlar S et al. 2011. Synthesis and characterization of tunable poly(ethylene glycol): gelatin methacrylate composite hydrogels. Tissue Eng. A 17:1713–23
    [Google Scholar]
  104. 104.  Suri S, Schmidt CE 2010. Cell-laden hydrogel constructs of hyaluronic acid, collagen, and laminin for neural tissue engineering. Tissue Eng. A 16:1703–16
    [Google Scholar]
  105. 105.  Tarus D, Hamard L, Caraguel F, Wion D, Szarpak-Jankowska A et al. 2016. Design of hyaluronic acid hydrogels to promote neurite outgrowth in three dimensions. ACS Appl. Mater. Interfaces 8:25051–59
    [Google Scholar]
  106. 106.  Wei Z, Lewis DM, Xu Y, Gerecht S 2017. Dual cross-linked biofunctional and self-healing networks to generate user-defined modular gradient hydrogel constructs. Adv. Healthc. Mater. 6:1700523
    [Google Scholar]
  107. 107.  Mason BN, Starchenko A, Williams RM, Bonassar LJ, Reinhart-King CA 2013. Tuning three-dimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior. Acta Biomater 9:4635–44
    [Google Scholar]
  108. 108.  Francis-Sedlak ME, Uriel S, Larson JC, Greisler HP, Venerus DC, Brey EM 2009. Characterization of type I collagen gels modified by glycation. Biomaterials 30:1851–56
    [Google Scholar]
  109. 109.  Jiang L, Sun Z, Chen X, Li J, Xu Y et al. 2016. Cells sensing mechanical cues: stiffness influences the lifetime of cell–extracellular matrix interactions by affecting the loading rate. ACS Nano 10:207–17
    [Google Scholar]
  110. 110.  Seong J, Tajik A, Sun J, Guan JL, Humphries MJ et al. 2013. Distinct biophysical mechanisms of focal adhesion kinase mechanoactivation by different extracellular matrix proteins. PNAS 110:19372–77
    [Google Scholar]
  111. 111.  Gandavarapu NR, Alge DL, Anseth KS 2014. Osteogenic differentiation of human mesenchymal stem cells on α5 integrin binding peptide hydrogels is dependent on substrate elasticity. Biomater. Sci. 2:352–61
    [Google Scholar]
  112. 112.  Ross RS 2004. Molecular and mechanical synergy: cross-talk between integrins and growth factor receptors. Cardiovasc. Res. 63:381–90
    [Google Scholar]
  113. 113.  Lee YJ, Streuli CH 1999. Extracellular matrix selectively modulates the response of mammary epithelial cells to different soluble signaling ligands. J. Biol. Chem. 274:22401–8
    [Google Scholar]
  114. 114.  Rodriguez KJ, Masters KS 2009. Regulation of valvular interstitial cell calcification by components of the extracellular matrix. J. Biomed. Mater. Res. A 90:1043–53
    [Google Scholar]
  115. 115.  Pollock K, Jaraczewski TJ, Carroll MJ, Lebovic DI, Kreeger PK 2014. Endometriotic epithelial cell response to macrophage-secreted factors is dependent on extracellular matrix context. Cell Mol. Bioeng. 7:409–20
    [Google Scholar]
  116. 116.  Chai C, Leong KW 2007. Biomaterials approach to expand and direct differentiation of stem cells. Mol. Ther. 15:467–80
    [Google Scholar]
  117. 117.  Kilian KA, Mrksich M 2012. Directing stem cell fate by controlling the affinity and density of ligand–receptor interactions at the biomaterials interface. Angew. Chem. Int. Ed. Engl. 51:4891–95
    [Google Scholar]
  118. 118.  Zieris A, Prokoph S, Levental KR, Welzel PB, Grimmer M et al. 2010. FGF-2 and VEGF functionalization of starPEG–heparin hydrogels to modulate biomolecular and physical cues of angiogenesis. Biomaterials 31:7985–94
    [Google Scholar]
  119. 119.  Hanahan D, Weinberg RA 2000. The hallmarks of cancer. Cell 100:57–70
    [Google Scholar]
  120. 120.  Lin B, Yin T, Wu YI, Inoue T, Levchenko A 2015. Interplay between chemotaxis and contact inhibition of locomotion determines exploratory cell migration. Nat. Commun. 6:6619
    [Google Scholar]
  121. 121.  Foley JD, Grunwald EW, Nealey PF, Murphy CJ 2005. Cooperative modulation of neuritogenesis by PC12 cells by topography and nerve growth factor. Biomaterials 26:3639–44
    [Google Scholar]
  122. 122.  Raghunathan V, McKee C, Cheung W, Naik R, Nealey PF et al. 2013. Influence of extracellular matrix proteins and substratum topography on corneal epithelial cell alignment and migration. Tissue Eng. A 19:1713–22
    [Google Scholar]
  123. 123.  Tocce EJ, Liliensiek SJ, Broderick AH, Jiang Y, Murphy KC et al. 2013. The influence of biomimetic topographical features and the extracellular matrix peptide RGD on human corneal epithelial contact guidance. Acta Biomater 9:5040–51
    [Google Scholar]
  124. 124.  Kim DH, Provenzano PP, Smith CL, Levchenko A 2012. Matrix nanotopography as a regulator of cell function. J. Cell Biol. 197:351–60
    [Google Scholar]
  125. 125.  Cosgrove BD, Mui KL, Driscoll TP, Caliari SR, Mehta KD et al. 2016. N-Cadherin adhesive interactions modulate matrix mechanosensing and fate commitment of mesenchymal stem cells. Nat. Mater. 15:1297–306
    [Google Scholar]
  126. 126.  Ye K, Cao L, Li S, Yu L, Ding J 2016. Interplay of matrix stiffness and cell–cell contact in regulating differentiation of stem cells. ACS Appl. Mater. Interfaces 8:21903–13
    [Google Scholar]
  127. 127.  Mao AS, Shin JW, Mooney DJ 2016. Effects of substrate stiffness and cell–cell contact on mesenchymal stem cell differentiation. Biomaterials 98:184–91
    [Google Scholar]
  128. 128.  Flaim CJ, Teng D, Chien S, Bhatia SN 2008. Combinatorial signaling microenvironments for studying stem cell fate. Stem Cells Dev 17:29–39
    [Google Scholar]
  129. 129.  Ranga A, Gobaa S, Okawa Y, Mosiewicz K, Negro A, Lutolf MP 2014. 3D niche microarrays for systems-level analyses of cell fate. Nat. Commun. 5:4324
    [Google Scholar]
  130. 130.  Chen S, Bremer AW, Scheideler OJ, Na YS, Todhunter ME et al. 2016. Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities. Nat. Commun. 7:10309
    [Google Scholar]
  131. 131.  Rape AD, Zibinsky M, Murthy N, Kumar S 2015. A synthetic hydrogel for the high-throughput study of cell–ECM interactions. Nat. Commun. 6:8129
    [Google Scholar]
  132. 132.  Tang F, Barbacioru C, Wang Y, Nordman E, Lee C et al. 2009. mRNA-Seq whole-transcriptome analysis of a single cell. Nat. Methods 6:377–82
    [Google Scholar]
  133. 133.  Bendall SC, Simonds EF, Qiu P, Amir el AD, Krutzik PO et al. 2011. Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science 332:687–96
    [Google Scholar]
  134. 134.  Irish JM, Hovland R, Krutzik PO, Perez OD, Bruserud O et al. 2004. Single cell profiling of potentiated phospho-protein networks in cancer cells. Cell 118:217–28
    [Google Scholar]
  135. 135.  Gaudet S, Miller-Jensen K 2016. Redefining signaling pathways with an expanding single-cell toolbox. Trends Biotechnol 34:458–69
    [Google Scholar]
  136. 136.  Regot S, Hughey JJ, Bajar BT, Carrasco S, Covert MW 2014. High-sensitivity measurements of multiple kinase activities in live single cells. Cell 157:1724–34
    [Google Scholar]
  137. 137.  Albeck JG, Mills GB, Brugge JS 2013. Frequency-modulated pulses of ERK activity transmit quantitative proliferation signals. Mol. Cell 49:249–61
    [Google Scholar]
  138. 138.  Warren EA, Netterfield TS, Sarkar S, Kemp ML, Payne CK 2015. Spatially-resolved intracellular sensing of hydrogen peroxide in living cells. Sci. Rep. 5:16929
    [Google Scholar]
  139. 139.  Kniss-James AS, Rivet CA, Chingozha L, Lu H, Kemp ML 2017. Single-cell resolution of intracellular T cell Ca2+ dynamics in response to frequency-based H2O2 stimulation. Integr. Biol. 9:238–47
    [Google Scholar]
  140. 140.  Lee RE, Walker SR, Savery K, Frank DA, Gaudet S 2014. Fold change of nuclear NF-κB determines TNF-induced transcription in single cells. Mol. Cell 53:867–79
    [Google Scholar]
  141. 141.  Lu Y, Xue Q, Eisele MR, Sulistijo ES, Brower K et al. 2015. Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands. PNAS 112:E607–15
    [Google Scholar]
  142. 142.  Campagnola PJ, Loew LM 2003. Second-harmonic imaging microscopy for visualizing biomolecular arrays in cells, tissues and organisms. Nat. Biotechnol. 21:1356–60
    [Google Scholar]
  143. 143.  Notbohm J, Lesman A, Tirrell DA, Ravichandran G 2015. Quantifying cell-induced matrix deformation in three dimensions based on imaging matrix fibers. Integr. Biol. 7:1186–95
    [Google Scholar]
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