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Materials control of the epigenetics underlying cell plasticity

Nature Reviews Materials volume 6, pages 69–83 (2021)Cite this article

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Abstract

The dynamic epigenetic landscape directs gene expression patterns that dictate cellular form and function, and drive the assembly of cells into tissues. The high degree of plasticity in the epigenetic landscape of mammalian cells is directed by materials, which provide the context in which cells receive and integrate multivariate signals to programme the chromatin state towards specific functional outcomes. In this Review, we explore how materials guide the cellular epigenetic landscape and discuss how engineered materials target cell plasticity, particularly through dynamic changes in histone methylation and acetylation. After discussing findings in developmental biology and cancer research that link materials parameters to chromatin state, we highlight how cell culture materials that control ligand presentation, mechanics, topography and geometry have shown how materials cues and context influence chromatin state through mechanotransduction. Finally, we describe how tissue fabrication can control cellular plasticity to drive meaningful biological activities that may facilitate the assembly of cells and tissues into functional architectures.

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Fig. 1: Chromatin modification and the epigenetic landscape in a materials context.
Fig. 2: The tissue microenvironment can dictate the epigenetic state.
Fig. 3: Mechanotransduction at the biomaterials interface.
Fig. 4: Engineering epigenetics using defined materials.
Fig. 5: Update to the tissue engineering paradigm.

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References

  1. Srivastava, P. & Kilian, K. A. Micro-engineered models of development using induced pluripotent stem cells. Front. Bioeng. Biotechnol. 7, 357 (2019).

    Article  Google Scholar 

  2. Rozario, T. & DeSimone, D. W. The extracellular matrix in development and morphogenesis: a dynamic view. Dev. Biol. 341, 126–140 (2010).

    Article  CAS  Google Scholar 

  3. Loganathan, R. et al. Extracellular matrix motion and early morphogenesis. Development 143, 2056–2065 (2016).

    Article  CAS  Google Scholar 

  4. Bhattacharjee, R., Moriam, S., Umer, M., Nguyen, N.-T. & Shiddiky, M. J. A. DNA methylation detection: recent developments in bisulfite free electrochemical and optical approaches. Analyst 143, 4802–4818 (2018).

    Article  CAS  Google Scholar 

  5. Furey, T. S. ChIP–seq and beyond: new and improved methodologies to detect and characterize protein–DNA interactions. Nat. Rev. Genet. 13, 840–852 (2012).

    Article  CAS  Google Scholar 

  6. Shi, L. & Wu, J. Epigenetic regulation in mammalian preimplantation embryo development. Reprod. Biol. Endocrinol. 7, 59 (2009).

    Article  CAS  Google Scholar 

  7. Esteller, M. Epigenetics in cancer. N. Engl. J. Med. 358, 1148–1159 (2008).

    Article  CAS  Google Scholar 

  8. Portela, A. & Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol. 28, 1057–1068 (2010).

    Article  CAS  Google Scholar 

  9. Egger, G., Liang, G., Aparicio, A. & Jones, P. A. Epigenetics in human disease and prospects for epigenetic therapy. Nature 429, 457–463 (2004).

    Article  CAS  Google Scholar 

  10. Feinberg, A. P. Phenotypic plasticity and the epigenetics of human disease. Nature 447, 433–440 (2007).

    Article  CAS  Google Scholar 

  11. Hansen, K. D. et al. Increased methylation variation in epigenetic domains across cancer types. Nat. Genet. 43, 768–775 (2011).

    Article  CAS  Google Scholar 

  12. Holoch, D. & Moazed, D. RNA-mediated epigenetic regulation of gene expression. Nat. Rev. Genet. 16, 71–84 (2015).

    Article  CAS  Google Scholar 

  13. Cole, P. A. Chemical probes for histone-modifying enzymes. Nat. Chem. Biol. 4, 590–597 (2008).

    Article  CAS  Google Scholar 

  14. Bonasio, R., Tu, S. & Reinberg, D. Molecular signals of epigenetic states. Science 330, 612–616 (2010).

    Article  CAS  Google Scholar 

  15. Badeaux, A. I. & Shi, Y. Emerging roles for chromatin as a signal integration and storage platform. Nat. Rev. Mol. Cell Biol. 14, 211–224 (2013).

    Article  CAS  Google Scholar 

  16. Fagnocchi, L., Mazzoleni, S. & Zippo, A. Integration of signaling pathways with the epigenetic machinery in the maintenance of stem cells. Stem Cell Int. 2016, 13 (2016).

    Google Scholar 

  17. Spencer, V. A., Xu, R. & Bissell, M. J. in Advances in Cancer Research Vol. 97 (eds Vande Woude, G. F. & Klein, G.) 275-294 (Academic, 2007).

  18. Chang, C. P. & Bruneau, B. G. Epigenetics and cardiovascular development. Annu. Rev. Physiol. 74, 41–68 (2012).

    Article  CAS  Google Scholar 

  19. Ho, L. et al. An embryonic stem cell chromatin remodeling complex, esBAF, is essential for embryonic stem cell self-renewal and pluripotency. Proc. Natl Acad. Sci. USA 106, 5181–5186 (2009).

    Article  CAS  Google Scholar 

  20. Lickert, H. et al. Baf60c is essential for function of BAF chromatin remodelling complexes in heart development. Nature 432, 107–112 (2004).

    Article  CAS  Google Scholar 

  21. Choi, Y. Y. et al. Controlled-size embryoid body formation in concave microwell arrays. Biomaterials 31, 4296–4303 (2010).

    Article  CAS  Google Scholar 

  22. Bonnans, C., Chou, J. & Werb, Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 15, 786–801 (2014).

    Article  CAS  Google Scholar 

  23. Vigetti, D. et al. Epigenetics in extracellular matrix remodeling and hyaluronan metabolism. FEBS J. 281, 4980–4992 (2014).

    Article  CAS  Google Scholar 

  24. Tibbitt, M. W. & Anseth, K. S. Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol. Bioeng. 103, 655–663 (2009).

    Article  CAS  Google Scholar 

  25. Engler, A. J., Sen, S., Sweeney, H. L. & Discher, D. E. Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006).

    Article  CAS  Google Scholar 

  26. Discher, D. E., Janmey, P. & Wang, Y.-L. Tissue cells feel and respond to the stiffness of their substrate. Science 310, 1139–1143 (2005).

    Article  CAS  Google Scholar 

  27. Chen, C. S., Mrksich, M., Huang, S., Whitesides, G. M. & Ingber, D. E. Geometric control of cell life and death. Science 276, 1425–1428 (1997).

    Article  CAS  Google Scholar 

  28. Levental, K. R. et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139, 891–906 (2009).

    Article  CAS  Google Scholar 

  29. Discher, D. E. et al. Matrix mechanosensing: from scaling concepts in ’omics data to mechanisms in the nucleus, regeneration, and cancer. Annu. Rev. Biophys. 46, 295–315 (2017).

    Article  CAS  Google Scholar 

  30. Madl, C. M. & Heilshorn, S. C. Engineering hydrogel microenvironments to recapitulate the stem cell niche. Annu. Rev. Biomed. Eng. 20, 21–47 (2018).

    Article  CAS  Google Scholar 

  31. Li, W., Yan, Z., Ren, J. & Qu, X. Manipulating cell fate: dynamic control of cell behaviors on functional platforms. Chem. Soc. Rev. 47, 8639–8684 (2018).

    Article  CAS  Google Scholar 

  32. Donnelly, H., Salmeron-Sanchez, M. & Dalby, M. J. Designing stem cell niches for differentiation and self-renewal. J. R. Soc. Interface 15, 20180388 (2018).

    Article  CAS  Google Scholar 

  33. Vining, K. H. & Mooney, D. J. Mechanical forces direct stem cell behaviour in development and regeneration. Nat. Rev. Mol. Cell Biol. 18, 728–742 (2017).

    Article  CAS  Google Scholar 

  34. Qu, F. et al. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface. Biomaterials 39, 85–94 (2015).

    Article  CAS  Google Scholar 

  35. Long, J., Kim, H., Kim, D., Lee, J. B. & Kim, D. H. A biomaterial approach to cell reprogramming and differentiation. J. Mater. Chem. B 5, 2375–2379 (2017).

    Article  CAS  Google Scholar 

  36. Shivashankar, G. V. Mechanical regulation of genome architecture and cell-fate decisions. Curr. Opin. Cell Biol. 56, 115–121 (2019).

    Article  CAS  Google Scholar 

  37. Spagnol, S. T. & Dahl, K. N. Spatially resolved quantification of chromatin condensation through differential local rheology in cell nuclei fluorescence lifetime imaging. PLoS ONE 11, e0146244 (2016).

    Article  CAS  Google Scholar 

  38. Song, Y., Soto, J., Chen, B., Yang, L. & Li, S. Cell engineering biophysical regulation of the nucleus. Biomaterials 234, 119743 (2020).

    Article  CAS  Google Scholar 

  39. Peng, Q. et al. Coordinated histone modifications and chromatin reorganization in a single cell revealed by FRET biosensors. Proc. Natl Acad. Sci. USA 115, E11681–E11690 (2018).

    Article  CAS  Google Scholar 

  40. Gurard-Levin, Z. A., Kilian, K. A., Kim, J., Bähr, K. & Mrksich, M. Peptide arrays identify isoform-selective substrates for profiling endogenous lysine deacetylase activity. ACS Chem. Biol. 5, 863–873 (2010).

    Article  CAS  Google Scholar 

  41. Szczesny, S. E. & Mauck, R. L. The nuclear option: evidence implicating the cell nucleus in mechanotransduction. J. Biomech. Eng. 139, 021006 (2017).

    Article  Google Scholar 

  42. Kouzarides, T. Chromatin modifications and their function. Cell 128, 693–705 (2007).

    Article  CAS  Google Scholar 

  43. Kim, T. H. et al. A high-resolution map of active promoters in the human genome. Nature 436, 876–880 (2005).

    Article  CAS  Google Scholar 

  44. Papp, B. & Muller, J. Histone trimethylation and the maintenance of transcriptional ON and OFF states by trxG and PcG proteins. Genes Dev. 20, 2041–2054 (2006).

    Article  CAS  Google Scholar 

  45. Butler, J. S., Koutelou, E., Schibler, A. C. & Dent, S. Y. Histone-modifying enzymes: regulators of developmental decisions and drivers of human disease. Epigenomics 4, 163–177 (2012).

    Article  CAS  Google Scholar 

  46. D’Urso, A. & Brickner, J. H. Mechanisms of epigenetic memory. Trends Genet. 30, 230–236 (2014).

    Article  CAS  Google Scholar 

  47. Zhu, B. & Reinberg, D. Epigenetic inheritance: uncontested? Cell Res. 21, 435–441 (2011).

    Article  CAS  Google Scholar 

  48. Simon, J. A. & Tamkun, J. W. Programming off and on states in chromatin: mechanisms of Polycomb and trithorax group complexes. Curr. Opin. Genet. Dev. 12, 210–218 (2002).

    Article  CAS  Google Scholar 

  49. Hansen, K. H. et al. A model for transmission of the H3K27me3 epigenetic mark. Nat. Cell Biol. 10, 1291–1300 (2008).

    Article  CAS  Google Scholar 

  50. Klosin, A., Casas, E., Hidalgo-Carcedo, C., Vavouri, T. & Lehner, B. Transgenerational transmission of environmental information in C. elegans. Science 356, 320–323 (2017).

    Article  CAS  Google Scholar 

  51. Waddington, C. H. The Strategy of the Genes (Allen & Unwin, 1957).

  52. Jablonka, E. & Lamb, M. J. The changing concept of epigenetics. Ann. N. Y. Acad. Sci. 981, 82–96 (2002).

    Article  Google Scholar 

  53. Santos, F., Hendrich, B., Reik, W. & Dean, W. Dynamic reprogramming of DNA methylation in the early mouse embryo. Dev. Biol. 241, 172–182 (2002).

    Article  CAS  Google Scholar 

  54. Li, E. Chromatin modification and epigenetic reprogramming in mammalian development. Nat. Rev. Genet. 3, 662–673 (2002).

    Article  CAS  Google Scholar 

  55. Feldman, N. et al. G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis. Nat. Cell Biol. 8, 188–194 (2006).

    Article  CAS  Google Scholar 

  56. Schleithoff, C., Voelter-Mahlknecht, S., Dahmke, I. N. & Mahlknecht, U. On the epigenetics of vascular regulation and disease. Clin. Epigenetics 4, 7 (2012).

    Article  Google Scholar 

  57. van Weerd, J. H., Koshiba-Takeuchi, K., Kwon, C. & Takeuchi, J. K. Epigenetic factors and cardiac development. Cardiovasc. Res. 91, 203–211 (2011).

    Article  CAS  Google Scholar 

  58. Yuan, X. & Braun, T. Multimodal regulation of cardiac myocyte proliferation. Circ. Res. 121, 293–309 (2017).

    Article  CAS  Google Scholar 

  59. Cui, M., Wang, Z., Bassel-Duby, R. & Olson, E. N. Genetic and epigenetic regulation of cardiomyocytes in development, regeneration and disease. Development 145, dev171983 (2018).

    Article  CAS  Google Scholar 

  60. Anier, K. & Kalda, A. Epigenetics in the central nervous system. Curr. Geriatr. Rep. 1, 190–198 (2012).

    Article  CAS  Google Scholar 

  61. Hagood, J. S. Beyond the genome: epigenetic mechanisms in lung remodeling. Physiology 29, 177–185 (2014).

    Article  CAS  Google Scholar 

  62. Park-Min, K. H. Epigenetic regulation of bone cells. Connect. Tissue Res. 58, 76–89 (2017).

    Article  CAS  Google Scholar 

  63. Ogino, S. et al. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease. Mod. Pathol. 26, 465–484 (2013).

    Article  CAS  Google Scholar 

  64. Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061–1068 (2008).

    Article  CAS  Google Scholar 

  65. Kraft, A. & Rubin, B. P. Changing cells: An analysis of the concept of plasticity in the context of cellular differentiation. BioSocieties 11, 497–525 (2016).

    Article  Google Scholar 

  66. Yuan, S., Norgard, R. J. & Stanger, B. Z. Cellular plasticity in cancer. Cancer Discov. 9, 837–851 (2019).

    Article  CAS  Google Scholar 

  67. Okita, K., Ichisaka, T. & Yamanaka, S. Generation of germline-competent induced pluripotent stem cells. Nature 448, 313–317 (2007).

    Article  CAS  Google Scholar 

  68. Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663–676 (2006). This was the first study to demonstrate the reprogramming of somatic cells into a pluripotent state (IPS cells) using lentivirus transcription factors that effectively reset the epigenome.

    Article  CAS  Google Scholar 

  69. Yu, J. et al. Induced pluripotent stem cell lines derived from human somatic cells. Science 318, 1917–1920 (2007).

    Article  CAS  Google Scholar 

  70. Buganim, Y., Faddah, D. A. & Jaenisch, R. Mechanisms and models of somatic cell reprogramming. Nat. Rev. Genet. 14, 427–439 (2013).

    Article  CAS  Google Scholar 

  71. Golipour, A. et al. A late transition in somatic cell reprogramming requires regulators distinct from the pluripotency network. Cell Stem Cell 11, 769–782 (2012).

    Article  CAS  Google Scholar 

  72. Polo, J. M. et al. A molecular roadmap of reprogramming somatic cells into iPS cells. Cell 151, 1617–1632 (2012).

    Article  CAS  Google Scholar 

  73. Buganim, Y. et al. Single-cell expression analyses during cellular reprogramming reveal an early stochastic and a late hierarchic phase. Cell 150, 1209–1222 (2012).

    Article  CAS  Google Scholar 

  74. Brambrink, T. et al. Sequential expression of pluripotency markers during direct reprogramming of mouse somatic cells. Cell Stem Cell 2, 151–159 (2008).

    Article  CAS  Google Scholar 

  75. Sridharan, R. et al. Role of the murine reprogramming factors in the induction of pluripotency. Cell 136, 364–377 (2009).

    Article  CAS  Google Scholar 

  76. Silva, J. et al. Nanog is the gateway to the pluripotent ground state. Cell 138, 722–737 (2009).

    Article  CAS  Google Scholar 

  77. Singhal, N. et al. Chromatin-remodeling components of the BAF complex facilitate reprogramming. Cell 141, 943–955 (2010).

    Article  CAS  Google Scholar 

  78. Maherali, N. et al. Directly reprogrammed fibroblasts show global epigenetic remodeling and widespread tissue contribution. Cell Stem Cell 1, 55–70 (2007).

    Article  CAS  Google Scholar 

  79. Kim, J. B. et al. Oct4-induced pluripotency in adult neural stem cells. Cell 136, 411–419 (2009).

    Article  CAS  Google Scholar 

  80. Woltjen, K. et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766–770 (2009).

    Article  CAS  Google Scholar 

  81. Zhou, H. et al. Generation of induced pluripotent stem cells using recombinant proteins. Cell Stem Cell 4, 381–384 (2009).

    Article  CAS  Google Scholar 

  82. Warren, L. et al. Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA. Cell Stem Cell 7, 618–630 (2010).

    Article  CAS  Google Scholar 

  83. Yuan, X., Li, W. & Ding, S. Small molecules in cellular reprogramming and differentiation. Prog. Drug Res. 67, 253–266 (2011).

    CAS  Google Scholar 

  84. Feng, B., Ng, J.-H., Heng, J.-C. D. & Ng, H.-H. Molecules that promote or enhance reprogramming of somatic cells to induced pluripotent stem cells. Cell Stem Cell 4, 301–312 (2009).

    Article  CAS  Google Scholar 

  85. Hou, P. et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science 341, 651–654 (2013).

    Article  CAS  Google Scholar 

  86. Frantz, C., Stewart, K. M. & Weaver, V. M. The extracellular matrix at a glance. J. Cell Sci. 123, 4195–4200 (2010).

    Article  CAS  Google Scholar 

  87. Razafiarison, T. et al. Biomaterial surface energy-driven ligand assembly strongly regulates stem cell mechanosensitivity and fate on very soft substrates. Proc. Natl Acad. Sci. USA 115, 4631–4636 (2018).

    Article  CAS  Google Scholar 

  88. Juliano, R. L. Signal transduction by cell adhesion receptors and the cytoskeleton: functions of integrins, cadherins, selectins, and immunoglobulin-superfamily members. Annu. Rev. Pharmacol. Toxicol. 42, 283–323 (2002).

    Article  CAS  Google Scholar 

  89. Horton, E. R. et al. The integrin adhesome network at a glance. J. Cell Sci. 129, 4159–4163 (2016).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  91. Lam, R. M. & Chesler, A. T. Shear elegance: A novel screen uncovers a mechanosensitive GPCR. J. Gen. Physiol. 150, 907–910 (2018).

    Article  CAS  Google Scholar 

  92. Cox, C. D., Bavi, N. & Martinac, B. Biophysical principles of ion-channel-mediated mechanosensory transduction. Cell Rep. 29, 1–12 (2019).

    Article  CAS  Google Scholar 

  93. Arcangeli, A. & Becchetti, A. Complex functional interaction between integrin receptors and ion channels. Trends Cell Biol. 16, 631–639 (2006).

    Article  CAS  Google Scholar 

  94. Patkunarajah, A. et al. TMEM87a/Elkin1, a component of a novel mechanoelectrical transduction pathway, modulates melanoma adhesion and migration. eLife 9, e53308 (2020).

    Article  Google Scholar 

  95. Pathak, M. M. et al. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc. Natl Acad. Sci. USA 111, 16148–16153 (2014).

    Article  CAS  Google Scholar 

  96. Kechagia, J. Z., Ivaska, J. & Roca-Cusachs, P. Integrins as biomechanical sensors of the microenvironment. Nat. Rev. Mol. Cell Biol. 20, 457–473 (2019).

    Article  CAS  Google Scholar 

  97. Ventre, M., Causa, F. & Netti, P. A. Determinants of cell-material crosstalk at the interface: towards engineering of cell instructive materials. J. R. Soc. Interface 9, 2017–2032 (2012).

    Article  CAS  Google Scholar 

  98. Brown, A. E. X. & Discher, D. E. Conformational changes and signaling in cell and matrix physics. Curr. Biol. 19, R781–R789 (2009).

    Article  CAS  Google Scholar 

  99. Salvi, A. M. & DeMali, K. A. Mechanisms linking mechanotransduction and cell metabolism. Curr. Opin. Cell Biol. 54, 114–120 (2018).

    Article  CAS  Google Scholar 

  100. Asparuhova, M. B., Gelman, L. & Chiquet, M. Role of the actin cytoskeleton in tuning cellular responses to external mechanical stress. Scand. J. Med. Sci. Sports 19, 490–499 (2009).

    Article  CAS  Google Scholar 

  101. Martino, F., Perestrelo, A. R., Vinarský, V., Pagliari, S. & Forte, G. Cellular mechanotransduction: from tension to function. Front. Physiol. 9, 824 (2018).

    Article  Google Scholar 

  102. Bissell, M. J., Hall, H. G. & Parry, G. How does the extracellular matrix direct gene expression? J. Theor. Biol. 99, 31–68 (1982). This is the first description of ‘dynamic reciprocity’ between the ECM and the cytoskeleton and nucleus, and of how this relates to the regulation of gene expression.

    Article  CAS  Google Scholar 

  103. Thorne, J. T. et al. Dynamic reciprocity between cells and their microenvironment in reproduction. Biol. Reprod. 92, 25 (2015).

    Article  CAS  Google Scholar 

  104. Schultz, G. S., Davidson, J. M., Kirsner, R. S., Bornstein, P. & Herman, I. M. Dynamic reciprocity in the wound microenvironment. Wound Repair. Regen. 19, 134–148 (2011).

    Article  Google Scholar 

  105. Xu, R., Boudreau, A. & Bissell, M. J. Tissue architecture and function: dynamic reciprocity via extra- and intra-cellular matrices. Cancer Metastasis Rev. 28, 167–176 (2009).

    Article  Google Scholar 

  106. Kim, H. Y. & Nelson, C. M. Extracellular matrix and cytoskeletal dynamics during branching morphogenesis. Organogenesis 8, 56–64 (2012).

    Article  Google Scholar 

  107. Zhou, J., Yi, Q. & Tang, L. The roles of nuclear focal adhesion kinase (FAK) on cancer: a focused review. J. Exp. Clin. Cancer Res. 38, 250 (2019).

    Article  Google Scholar 

  108. Maik-Rachline, G., Hacohen-Lev-Ran, A. & Seger, R. Nuclear ERK: Mechanism of translocation, substrates, and role in cancer. Int. J. Mol. Sci. 20, 1194 (2019).

    Article  CAS  Google Scholar 

  109. Wang, P. et al. WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment. Proc. Natl Acad. Sci. USA 115, 8581–8586 (2018).

    Article  CAS  Google Scholar 

  110. Dupont, S. et al. Role of YAP/TAZ in mechanotransduction. Nature 474, 179–183 (2011).

    Article  CAS  Google Scholar 

  111. Elosegui-Artola, A. et al. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell 171, 1397–1410 e14 (2017). This study demonstrates how matrix mechanics dictates coupling between the cytoskeleton and the nucleus to stretch nuclear pores and regulate import of the mechanosensor and transcriptional activator YAP.

    Article  CAS  Google Scholar 

  112. Nardone, G. et al. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat. Commun. 8, 15321 (2017).

    Article  CAS  Google Scholar 

  113. Uhler, C. & Shivashankar, G. V. Regulation of genome organization and gene expression by nuclear mechanotransduction. Nat. Rev. Mol. Cell Biol. 18, 717–727 (2017).

    Article  CAS  Google Scholar 

  114. Shiu, J. Y., Aires, L., Lin, Z. & Vogel, V. Nanopillar force measurements reveal actin-cap-mediated YAP mechanotransduction. Nat. Cell Biol. 20, 262–271 (2018).

    Article  CAS  Google Scholar 

  115. Denais, C. M. et al. Nuclear envelope rupture and repair during cancer cell migration. Science 352, 353–358 (2016). This study shows how cell migration through confined environments can rupture the nucleus, with evidence that nuclear lamin content contributes to nuclear stability under stress.

    Article  CAS  Google Scholar 

  116. Totaro, A., Panciera, T. & Piccolo, S. YAP/TAZ upstream signals and downstream responses. Nat. Cell Biol. 20, 888–899 (2018).

    Article  CAS  Google Scholar 

  117. Wang, N., Tytell, J. D. & Ingber, D. E. Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat. Rev. Mol. Cell Biol. 10, 75–82 (2009).

    Article  CAS  Google Scholar 

  118. Enyedi, B., Jelcic, M. & Niethammer, P. The cell nucleus serves as a mechanotransducer of tissue damage-induced inflammation. Cell 165, 1160–1170 (2016).

    Article  CAS  Google Scholar 

  119. Irianto, J., Ivanovska, I. L., Swift, J. & Discher, D. E. in Molecular and Cellular Mechanobiology Ch. 9 (eds Chien, S., Engler, A. J. & Wang, P. Y.) 175–195 (Springer, 2016).

  120. Lombardi, M. L. et al. The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J. Biol. Chem. 286, 26743–26753 (2011).

    Article  CAS  Google Scholar 

  121. Caille, N., Tardy, Y. & Meister, J. J. Assessment of strain field in endothelial cells subjected to uniaxial deformation of their substrate. Ann. Biomed. Eng. 26, 409–416 (1998).

    Article  CAS  Google Scholar 

  122. Booth-Gauthier, E. A., Alcoser, Turi, A., Yang, G. & Dahl, K. N. Force-induced changes in subnuclear movement and rheology. Biophys. J. 103, 2423–2431 (2012).

    Article  CAS  Google Scholar 

  123. Poh, Y.-C. et al. Dynamic force-induced direct dissociation of protein complexes in a nuclear body in living cells. Nat. Commun. 3, 866 (2012).

    Article  CAS  Google Scholar 

  124. Swift, J. et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341, 1240104 (2013). This study reveals a power-law scaling between ECM and tissue stiffness and nuclear lamin A levels, and how this dictates tissue-specific differentiation.

    Article  CAS  Google Scholar 

  125. Ihalainen, T. O. et al. Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension. Nat. Mater. 14, 1252–1261 (2015). This study demonstrates how force from the cytoskeleton during cell spreading influences chromatin accessibility through cytoskeleton–nucleoskeleton engagement of specific lamin A/C epitopes.

    Article  CAS  Google Scholar 

  126. Arsenovic, P. T. et al. Nesprin-2G, a component of the nuclear LINC complex, is subject to myosin-dependent tension. Biophys. J. 110, 34–43 (2016).

    Article  CAS  Google Scholar 

  127. Le, H. Q. et al. Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nat. Cell Biol. 18, 864–875 (2016). This study identifies the mechanosensory complex of emerin, non-muscle myosin IIA and actin in coordinating H3K9me to regulate transcription in response to force.

    Article  CAS  Google Scholar 

  128. Chambliss, A. B. et al. The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction. Sci. Rep. 3, 1087 (2013).

    Article  CAS  Google Scholar 

  129. Kim, D. H. & Wirtz, D. Cytoskeletal tension induces the polarized architecture of the nucleus. Biomaterials 48, 161–172 (2015).

    Article  CAS  Google Scholar 

  130. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nat. Rev. Mol. Cell Biol. 7, 265–275 (2006).

    Article  CAS  Google Scholar 

  131. Kononen, J. et al. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat. Med. 4, 844–847 (1998).

    Article  CAS  Google Scholar 

  132. Lutolf, M. P. & Hubbell, J. A. Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering. Nat. Biotechnol. 23, 47–55 (2005).

    Article  CAS  Google Scholar 

  133. Kratochvil, M. J. et al. Engineered materials for organoid systems. Nat. Rev. Mater. 4, 606–622 (2019).

    Article  CAS  Google Scholar 

  134. Hussey, G. S., Dziki, J. L. & Badylak, S. F. Extracellular matrix-based materials for regenerative medicine. Nat. Rev. Mater. 3, 159–173 (2018).

    Article  CAS  Google Scholar 

  135. Chiang, M. Y. M., Yangben, Y. Z., Lin, N. J., Zhong, J. L. L. & Yang, L. Relationships among cell morphology, intrinsic cell stiffness and cell-substrate interactions. Biomaterials 34, 9754–9762 (2013).

    Article  CAS  Google Scholar 

  136. Dingal, P. C. & Discher, D. E. Material control of stem cell differentiation: challenges in nano-characterization. Curr. Opin. Biotechnol. 28, 46–50 (2014).

    Article  CAS  Google Scholar 

  137. Yang, Y., Wang, K., Gu, X. S. & Leong, K. W. Biophysical regulation of cell behavior-cross talk between substrate stiffness and nanotopography. Engineering 3, 36–54 (2017).

    Article  CAS  Google Scholar 

  138. Core, L. J., Waterfall, J. J. & Lis, J. T. Nascent RNA sequencing reveals widespread pausing and divergent initiation at human promoters. Science 322, 1845–1848 (2008).

    Article  CAS  Google Scholar 

  139. Schuettengruber, B., Chourrout, D., Vervoort, M., Leblanc, B. & Cavalli, G. Genome regulation by polycomb and trithorax proteins. Cell 128, 735–745 (2007).

    Article  CAS  Google Scholar 

  140. Crowder, S. W., Leonardo, V., Whittaker, T., Papathanasiou, P. & Stevens, M. M. Material cues as potent regulators of epigenetics and stem cell function. Cell Stem Cell 18, 39–52 (2016).

    Article  CAS  Google Scholar 

  141. Larsson, L., Pilipchuk, S. P., Giannobile, W. V. & Castilho, R. M. When epigenetics meets bioengineering-A material characteristics and surface topography perspective. J. Biomed. Mater. Res. B Appl. Biomater. 106, 2065–2071 (2018).

    Article  CAS  Google Scholar 

  142. Illi, B. et al. Epigenetic histone modification and cardiovascular lineage programming in mouse embryonic stem cells exposed to laminar shear stress. Circ. Res. 96, 501–508 (2005).

    Article  CAS  Google Scholar 

  143. Zhou, J., Li, Y.-S., Wang, K.-C. & Chien, S. Epigenetic mechanism in regulation of endothelial function by disturbed flow: induction of DNA hypermethylation by DNMT1. Cell. Mol. Bioeng. 7, 218–224 (2014).

    Article  CAS  Google Scholar 

  144. Morgan, J. T. et al. Integration of basal topographic cues and apical shear stress in vascular endothelial cells. Biomaterials 33, 4126–4135 (2012).

    Article  CAS  Google Scholar 

  145. Dolberg, D. S. & Bissell, M. J. Inability of Rous sarcoma virus to cause sarcomas in the avian embryo. Nature 309, 552–556 (1984).

    Article  CAS  Google Scholar 

  146. Hendrix, M. J. C. et al. Reprogramming metastatic tumor cells with embryonic microenvironments. Nat. Rev. Cancer 7, 246–255 (2007).

    Article  CAS  Google Scholar 

  147. Postovit, L.-M., Seftor, E. A., Seftor, R. E. B. & Hendrix, M. J. C. A three-dimensional model to study the epigenetic effects induced by the microenvironment of human embryonic stem cells. Stem Cell 24, 501–505 (2006).

    Article  CAS  Google Scholar 

  148. Han, J., Sachdev, P. S. & Sidhu, K. S. A combined epigenetic and non-genetic approach for reprogramming human somatic cells. PLoS ONE 5, e12297 (2010).

    Article  CAS  Google Scholar 

  149. Anderson, D. G., Levenberg, S. & Langer, R. Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells. Nat. Biotechnol. 22, 863–866 (2004).

    Article  CAS  Google Scholar 

  150. Orner, B. P., Derda, R., Lewis, R. L., Thomson, J. A. & Kiessling, L. L. Arrays for the combinatorial exploration of cell adhesion. J. Am. Chem. Soc. 126, 10808–10809 (2004).

    Article  CAS  Google Scholar 

  151. Derda, R. et al. High-throughput discovery of synthetic surfaces that support proliferation of pluripotent cells. J. Am. Chem. Soc. 132, 1289–1295 (2010).

    Article  CAS  Google Scholar 

  152. Reticker-Flynn, N. E. et al. A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis. Nat. Commun. 3, 1122 (2012).

    Article  CAS  Google Scholar 

  153. Barney, L. E. et al. A cell–ECM screening method to predict breast cancer metastasis. Integr. Biol. 7, 198–212 (2014).

    Article  CAS  Google Scholar 

  154. Zhang, D. & Kilian, K. A. Peptide microarrays for the discovery of bioactive surfaces that guide cellular processes: a single step azide–alkyne “click” chemistry approach. J. Mater. Chem. B 2, 4280–4288 (2014).

    Article  CAS  Google Scholar 

  155. Zhang, D., Sun, M. B., Lee, J., Abdeen, A. A. & Kilian, K. A. Cell shape and the presentation of adhesion ligands guide smooth muscle myogenesis. J. Biomed. Mater. Res. A 104, 1212–1220 (2016).

    Article  CAS  Google Scholar 

  156. Zhang, D. et al. Combinatorial discovery of defined substrates that promote a stem cell state in malignant melanoma. ACS Cent. Sci. 3, 381–393 (2017).

    Article  CAS  Google Scholar 

  157. Kilian, K. A. & Mrksich, M. Directing stem cell fate by controlling the affinity and density of ligand–receptor interactions at the biomaterials interface. Angew. Chem. Int. Ed. Engl. 51, 4891–4895 (2012).

    Article  CAS  Google Scholar 

  158. Tajik, A. et al. Transcription upregulation via force-induced direct stretching of chromatin. Nat. Mater. 15, 1287–1296 (2016).

    Article  CAS  Google Scholar 

  159. Hersel, U., Dahmen, C. & Kessler, H. RGD modified polymers: biomaterials for stimulated cell adhesion and beyond. Biomaterials 24, 4385–4415 (2003).

    Article  CAS  Google Scholar 

  160. Maheshwari, G., Brown, G., Lauffenburger, D. A., Wells, A. & Griffith, L. G. Cell adhesion and motility depend on nanoscale RGD clustering. J. Cell Sci. 113, 1677–1686 (2000).

    CAS  Google Scholar 

  161. McKinnon, D. D., Domaille, D. W., Cha, J. N. & Anseth, K. S. Biophysically defined and cytocompatible covalently adaptable networks as viscoelastic 3D cell culture systems. Adv. Mater. 26, 865–872 (2014).

    Article  CAS  Google Scholar 

  162. Chaudhuri, O. Viscoelastic hydrogels for 3D cell culture. Biomater. Sci. 5, 1480–1490 (2017).

    Article  CAS  Google Scholar 

  163. Pajerowski, J. D., Dahl, K. N., Zhong, F. L., Sammak, P. J. & Discher, D. E. Physical plasticity of the nucleus in stem cell differentiation. Proc. Natl Acad. Sci. USA 104, 15619–15624 (2007). This study uses micromanipulation of the nucleus to identify changes in nuclear rheology during stem cell differentiation and demonstrates relationships between nuclear deformability and chromatin rheology.

    Article  CAS  Google Scholar 

  164. Makhija, E., Jokhun, D. S. & Shivashankar, G. V. Nuclear deformability and telomere dynamics are regulated by cell geometric constraints. Proc. Natl Acad. Sci. USA 113, E32–E40 (2016).

    Article  CAS  Google Scholar 

  165. Kirby, T. J. & Lammerding, J. Emerging views of the nucleus as a cellular mechanosensor. Nat. Cell Biol. 20, 373–381 (2018).

    Article  CAS  Google Scholar 

  166. Stowers, R. S. et al. Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility. Nat. Biomed. Eng. 3, 1009–1019 (2019).

    Article  Google Scholar 

  167. Li, Y., Tang, C. B. & Kilian, K. A. Matrix mechanics influence fibroblast–myofibroblast transition by directing the localization of histone deacetylase 4. Cell Mol. Bioeng. 10, 405–415 (2017).

    Article  CAS  Google Scholar 

  168. Yang, C., Tibbitt, M. W., Basta, L. & Anseth, K. S. Mechanical memory and dosing influence stem cell fate. Nat. Mater. 13, 645–652 (2014).

    Article  CAS  Google Scholar 

  169. Killaars, A. R. et al. Extended exposure to stiff microenvironments leads to persistent chromatin remodeling in human mesenchymal stem cells. Adv. Sci. 6, 1801483 (2018).

    Article  CAS  Google Scholar 

  170. Choi, B. et al. Stiffness of hydrogels regulates cellular reprogramming efficiency through mesenchymal-to-epithelial transition and stemness markers. Macromol. Biosci. 16, 199–206 (2016). This study shows how increased matrix stiffness changes nuclear morphology and increases lamina-associated chromatin to direct epigenetic regulation of histone states associated with increased tumorigenicity in breast cancer.

    Article  CAS  Google Scholar 

  171. Frith, J. E. et al. Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling. Nat. Commun. 9, 257 (2018).

    Article  CAS  Google Scholar 

  172. Lee, J. Y. et al. YAP-independent mechanotransduction drives breast cancer progression. Nat. Commun. 10, 1848 (2019).

    Article  CAS  Google Scholar 

  173. Jolivet, G., Pantano, T. & Houdebine, L. M. Regulation by the extracellular matrix (ECM) of prolactin-induced alpha s1-casein gene expression in rabbit primary mammary cells: role of STAT5, C/EBP, and chromatin structure. J. Cell Biochem. 95, 313–327 (2005).

    Article  CAS  Google Scholar 

  174. Kocgozlu, L. et al. Selective and uncoupled role of substrate elasticity in the regulation of replication and transcription in epithelial cells. J. Cell Sci. 123, 29–39 (2010).

    Article  CAS  Google Scholar 

  175. Chaudhuri, O. et al. Hydrogels with tunable stress relaxation regulate stem cell fate and activity. Nat. Mater. 15, 326–334 (2016).

    Article  CAS  Google Scholar 

  176. Chaudhuri, O. et al. Substrate stress relaxation regulates cell spreading. Nat. Commun. 6, 6365 (2015).

    Article  CAS  Google Scholar 

  177. Wisdom, K. M. et al. Matrix mechanical plasticity regulates cancer cell migration through confining microenvironments. Nat. Commun. 9, 4144 (2018).

    Article  CAS  Google Scholar 

  178. Das, R. K., Gocheva, V., Hammink, R., Zouani, O. F. & Rowan, A. E. Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels. Nat. Mater. 15, 318–325 (2016).

    Article  CAS  Google Scholar 

  179. Brock, A. et al. Geometric determinants of directional cell motility revealed using microcontact printing. Langmuir 19, 1611–1617 (2003).

    Article  CAS  Google Scholar 

  180. Kim, D.-H., Provenzano, P. P., Smith, C. L. & Levchenko, A. Matrix nanotopography as a regulator of cell function. J. Cell Biol. 197, 351–360 (2012).

    Article  CAS  Google Scholar 

  181. Bettinger, C. J., Langer, R. & Borenstein, J. T. Engineering substrate topography at the micro- and nanoscale to control cell function. Angew. Chem. Int. Ed. Engl. 48, 5406–5415 (2009).

    Article  CAS  Google Scholar 

  182. Yim, E. K. F., Pang, S. W. & Leong, K. W. Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. Exp. Cell Res. 313, 1820–1829 (2007).

    Article  CAS  Google Scholar 

  183. Dalby, M. J. et al. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder. Nat. Mater. 6, 997–1003 (2007).

    Article  CAS  Google Scholar 

  184. Lv, L. et al. The epigenetic mechanisms of nanotopography-guided osteogenic differentiation of mesenchymal stem cells via high-throughput transcriptome sequencing. Int. J. Nanomed. 13, 5605–5623 (2018).

    Article  CAS  Google Scholar 

  185. Dalby, M. J., Gadegaard, N. & Oreffo, R. O. C. Harnessing nanotopography and integrin–matrix interactions to influence stem cell fate. Nat. Mater. 13, 558–569 (2014).

    Article  CAS  Google Scholar 

  186. Downing, T. L. et al. Biophysical regulation of epigenetic state and cell reprogramming. Nat. Mater. 12, 1154–1162 (2013). This study demonstrates how nanostructured and microstructured substrates control MET in somatic cells undergoing reprogramming to pluripotency, through a coordinated biophysical–epigenetic mechanism involving H3 acetylation and methylation.

    Article  CAS  Google Scholar 

  187. Li, Y. et al. Biophysical regulation of histone acetylation in mesenchymal stem cells. Biophys. J. 100, 1902–1909 (2011).

    Article  CAS  Google Scholar 

  188. Yoo, J. et al. Nanogrooved substrate promotes direct lineage reprogramming of fibroblasts to functional induced dopaminergic neurons. Biomaterials 45, 36–45 (2015).

    Article  CAS  Google Scholar 

  189. Théry, M. Micropatterning as a tool to decipher cell morphogenesis and functions. J. Cell Sci. 123, 4201–4213 (2010).

    Article  CAS  Google Scholar 

  190. Watt, F. M., Jordan, P. W. & O’Neill, C. H. Cell shape controls terminal differentiation of human epidermal keratinocytes. Proc. Natl Acad. Sci. USA 85, 5576–5580 (1988).

    Article  CAS  Google Scholar 

  191. Kilian, K. A., Bugarija, B., Lahn, B. T. & Mrksich, M. Geometric cues for directing the differentiation of mesenchymal stem cells. Proc. Natl Acad. Sci. USA 107, 4872–4877 (2010).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  193. Le Beyec, J. et al. Cell shape regulates global histone acetylation in human mammary epithelial cells. Exp. Cell Res. 313, 3066–3075 (2007). This is the first study to show how micropatterning can be used to study epigenetic changes in response to cell shape, with a demonstration that cell rounding induces broad deacetylation of histone 3 and histone 4, with concurrent reduction in gene expression.

    Article  CAS  Google Scholar 

  194. Abdeen, A. A., Lee, J., Li, Y. & Kilian, K. A. Cytoskeletal priming of mesenchymal stem cells to a medicinal phenotype. Regen. Eng. Transl. Med. 3, 5–14 (2017).

    Article  CAS  Google Scholar 

  195. Jain, N., Iyer, K. V., Kumar, A. & Shivashankar, G. V. Cell geometric constraints induce modular gene-expression patterns via redistribution of HDAC3 regulated by actomyosin contractility. Proc. Natl Acad. Sci. USA 110, 11349–11354 (2013). This study shows how controlling cell shape can lead to changes in gene expression as a function of actomyosin contractility and localization of HDAC3 and transcription factors.

    Article  CAS  Google Scholar 

  196. Roy, B. et al. Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors. Proc. Natl Acad. Sci. USA 115, E4741–E4750 (2018). This study uses microconfinement to epigenetically reprogramme fibroblast cells into suspended stem-cell-like aggregates, with evidence for H3K9ac at reprogramming promoters and demonstration of tri-lineage differentiation.

    Article  CAS  Google Scholar 

  197. Roy, B. et al. Fibroblast rejuvenation by mechanical reprogramming and redifferentiation. Proc. Natl Acad. Sci. USA 117, 10131–10141 (2020).

    Article  CAS  Google Scholar 

  198. Chhabra, S., Liu, L., Goh, R., Kong, X. & Warmflash, A. Dissecting the dynamics of signaling events in the BMP, WNT, and NODAL cascade during self-organized fate patterning in human gastruloids. PLoS Biol. 17, e3000498 (2019).

    Article  CAS  Google Scholar 

  199. Kusuma, S., Smith, Q., Facklam, A. & Gerecht, S. Micropattern size-dependent endothelial differentiation from a human induced pluripotent stem cell line. J. Tissue Eng. Regen. Med. 11, 855–861 (2017).

    Article  CAS  Google Scholar 

  200. Xue, X. et al. Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells. Nat. Mater. 17, 633–641 (2018).

    Article  CAS  Google Scholar 

  201. Ma, Z. et al. Self-organizing human cardiac microchambers mediated by geometric confinement. Nat. Commun. 6, 7413 (2015).

    Article  CAS  Google Scholar 

  202. Myers, F. B. et al. Robust pluripotent stem cell expansion and cardiomyocyte differentiation via geometric patterning. Integr. Biol. 5, 1495–1506 (2013).

    Article  CAS  Google Scholar 

  203. Lee, J., Abdeen, A. A., Wycislo, K. L., Fan, T. M. & Kilian, K. A. Interfacial geometry dictates cancer cell tumorigenicity. Nat. Mater. 15, 856–862 (2016).

    Article  CAS  Google Scholar 

  204. Lee, J. L. et al. Melanoma topology reveals a stem-like phenotype that promotes angiogenesis. Sci. Adv. 3, e1701350 (2017).

    Article  CAS  Google Scholar 

  205. Lee, J. et al. Geometric regulation of histone state directs melanoma reprogramming. Commun. Biol. 3, 341 (2020). This study investigates geometric cues at the periphery of melanoma-cell aggregates and finds that H3K9ac and H3K4me controls cancer stem-cell-like states through the epigenetic modifier PRDM14.

    Article  Google Scholar 

  206. Duval, K. et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology 32, 266–277 (2017).

    Article  CAS  Google Scholar 

  207. Mirbagheri, M. et al. Advanced cell culture platforms: a growing quest for emulating natural tissues. Mater. Horiz. 6, 45–71 (2019).

    Article  CAS  Google Scholar 

  208. Moroni, L. et al. Biofabrication strategies for 3D in vitro models and regenerative medicine. Nat. Rev. Mater. 3, 21–37 (2018).

    Article  CAS  Google Scholar 

  209. Lewis, C., Mardaryev, A., Sharov, A., Fessing, M. & Botchkarev, V. The epigenetic regulation of wound healing. Adv. Wound Care 3, 468–475 (2014).

    Article  Google Scholar 

  210. Tough, D. F., Rioja, I., Modis, L. K. & Prinjha, R. K. Epigenetic regulation of T cell memory: recalling therapeutic implications. Trends Immunol. 41, 29–45 (2020).

    Article  CAS  Google Scholar 

  211. Strzelecka, P. M., Ranzoni, A. M. & Cvejic, A. Dissecting human disease with single-cell omics: application in model systems and in the clinic. Dis. Models Mech. 41, dmm036525 (2018).

    Article  CAS  Google Scholar 

  212. Talwar, S., Jain, N. & Shivashankar, G. V. The regulation of gene expression during onset of differentiation by nuclear mechanical heterogeneity. Biomaterials 35, 2411–2419 (2014).

    Article  CAS  Google Scholar 

  213. Illi, B. et al. Shear stress-mediated chromatin remodeling provides molecular basis for flow-dependent regulation of gene expression. Circ. Res. 93, 155–161 (2003).

    Article  CAS  Google Scholar 

  214. Goodwin, S., McPherson, J. D. & McCombie, W. R. Coming of age: ten years of next-generation sequencing technologies. Nat. Rev. Genet. 17, 333–351 (2016).

    Article  CAS  Google Scholar 

  215. DeAngelis, J. T., Farrington, W. J. & Tollefsbol, T. O. An overview of epigenetic assays. Mol. Biotechnol. 38, 179–183 (2008).

    Article  CAS  Google Scholar 

  216. Laird, P. W. Principles and challenges of genome-wide DNA methylation analysis. Nat. Rev. Genet. 11, 191–203 (2010).

    Article  CAS  Google Scholar 

  217. Yan, F., Powell, D. R., Curtis, D. J. & Wong, N. C. From reads to insight: a hitchhiker’s guide to ATAC-seq data analysis. Genome Biol. 21, 22 (2020).

    Article  Google Scholar 

  218. Klemm, S. L., Shipony, Z. & Greenleaf, W. J. Chromatin accessibility and the regulatory epigenome. Nat. Rev. Genet. 20, 207–220 (2019).

    Article  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge financial support from the Australian Research Council grant no. FT180100417 and the National Health and Medical Research Council grant no. APP1185021.

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  1. School of Materials Science and Engineering, University of New South Wales, Sydney, NSW, Australia

    Stephanie Nemec & Kristopher A. Kilian

  2. School of Chemistry, Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, Australia

    Kristopher A. Kilian

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S.N. and K.A.K. researched data for the article, wrote the manuscript and contributed to the discussion of the content.

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Nemec, S., Kilian, K.A. Materials control of the epigenetics underlying cell plasticity. Nat Rev Mater 6, 69–83 (2021). https://doi.org/10.1038/s41578-020-00238-z

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