A review of the effects of extracellular matrix stiffness on cellular activity
DOI:
https://doi.org/10.47611/jsrhs.v13i2.6568Keywords:
Extracellular Matrix, Stiffness, Stem Cell Differentiation, Metastasis, Metabolic ReprogrammingAbstract
The extracellular matrix is a vital component of a cellular system. It is responsible for several metabolic processes within cells and its properties can have major effects on cellular activity. Recent research has begun to understand the role of physical interactions between the matrix and the cell on cellular growth and repair. In this work, we review the role of the stiffness of the extracellular matrix in determining cellular activity. We first review the effect on stem cell differentiation through the influence of cytoskeletal feedback loops and induced traction stresses. We then discuss the effects of metabolic reprogramming in tumor progression via molecular upregulation of YAP/TAZ and genetic expression. Finally, we highlight the effects of the stiffness gradient dictated by durotaxis and induced hypoxia on the rate of tumor progression. We hope this review sheds light on the major impact that the extracellular matrix has on various biological activities.
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Gattazzo F, Urciuolo A, Bonaldo P. Extracellular matrix: a dynamic microenvironment for stem cell niche. Biochim Biophys Acta. 2014 Aug;1840(8):2506-19. https://doi.org/10.1016/j.bbagen.2014.01.010.
Max Urbanczyk, Shannon L. Layland, Katja Schenke-Layland, The role of extracellular matrix in biomechanics and its impact on bioengineering of cells and 3D tissues, Matrix Biology, Volumes 85–86, 2020, Pages 1-14, ISSN 0945-053X, https://doi.org/10.1016/j.matbio.2019.11.005.
Nancy L. Halliday, James J. Tomasek, Mechanical Properties of the Extracellular Matrix Influence Fibronectin Fibril Assembly in Vitro, Experimental Cell Research, Volume 217, Issue 1, 1995, Pages 109-117, ISSN 0014-4827, https://doi.org/10.1006/excr.1995.1069.
Joshua R. Gershlak, Lauren D. Black, Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix, Experimental Cell Research, Volume 330, Issue 2, 2015, Pages 311-324, ISSN 0014-4827, https://doi.org/10.1016/j.yexcr.2014.09.007.
Kloxin, A.M., Tibbitt, M.W., Kasko, A.M., Fairbairn, J.A. and Anseth, K.S. (2010), Tunable Hydrogels for External Manipulation of Cellular Microenvironments through Controlled Photodegradation. Adv. Mater., 22: 61-66. https://doi.org/10.1002/adma.200900917
Gu, L., Mooney, D. Biomaterials and emerging anticancer therapeutics: engineering the microenvironment. Nat Rev Cancer 16, 56–66 (2016). https://doi.org/10.1038/nrc.2015.3
Huang, J., Zhang, L., Wan, D. et al. Extracellular matrix and its therapeutic potential for cancer treatment.Sig Transduct Target Ther 6, 153 (2021). https://doi.org/10.1038/s41392-021-00544-0
Wells, R.G. (2008), The role of matrix stiffness in regulating cell behavior. Hepatology, 47: 1394-1400. https://doi.org/10.1002/hep.22193
Nic D. Leipzig, Molly S. Shoichet, The effect of substrate stiffness on adult neural stem cell behavior, Biomaterials, Volume 30, Issue 36, 2009, Pages 6867-6878, ISSN 0142-9612, https://doi.org/10.1016/j.biomaterials.2009.09.002
Lv, H., Li, L., Sun, M. et al. Mechanism of regulation of stem cell differentiation by matrix stiffness. Stem Cell Res Ther 6, 103 (2015). https://doi.org/10.1186/s13287-015-0083-4
Ge H, Tian M, Pei Q, Tan F, Pei H. Extracellular Matrix Stiffness: New Areas Affecting Cell Metabolism. Front Oncol. 2021 Feb 24;11:631991, https://doi.org/10.3389/fonc.2021.631991
Liu QP, Luo Q, Deng B, Ju Y, Song GB. Stiffer Matrix Accelerates Migration of Hepatocellular Carcinoma Cells through Enhanced Aerobic Glycolysis Via the MAPK-YAP Signaling. Cancers (Basel). 2020 Feb 19;12(2):490, https://doi.org/10.3390/cancers12020490
Bertero, T., Oldham, W. M., Cottrill, K. A., Pisano, S., Vanderpool, R. R., Yu, Q., Zhao, J., Tai, Y., Tang, Y., Zhang, Y. Y., Rehman, S., Sugahara, M., Qi, Z., Gorcsan, J., 3rd, Vargas, S. O., Saggar, R., Saggar, R., Wallace, W. D., Ross, D. J., Haley, K. J., … Chan, S. Y. (2016). Vascular stiffness mechanoactivates YAP/TAZ-dependent glutaminolysis to drive pulmonary hypertension. The Journal of clinical investigation, 126(9), 3313–3335. https://doi.org/10.1172/JCI86387
Hu, Y., Shin, D. J., Pan, H., Lin, Z., Dreyfuss, J. M., Camargo, F. D., Miao, J., & Biddinger, S. B. (2017). YAP suppresses gluconeogenic gene expression through PGC1α. Hepatology (Baltimore, Md.), 66(6), 2029–2041. https://doi.org/10.1002/hep.29373
Deng, B., Zhao, Z., Kong, W. et al. Biological role of matrix stiffness in tumor growth and treatment. J Transl Med 20, 540 (2022). https://doi.org/10.1186/s12967-022-03768-y
Zaman, M. H., Trapani, L. M., Sieminski, A. L., MacKellar, D., Gong, H., Kamm, R. D., Wells, A., Lauffenburger, D. A., & Matsudaira, P. (2006). Migration of tumor cells in 3D matrices is governed by matrix stiffness along with cell-matrix adhesion and proteolysis. Proceedings of the National Academy of Sciences, 103(29), 10889-10894. https://doi.org/10.1073/pnas.0604460103
DuChez, B. J., Doyle, A. D., Dimitriadis, E. K., & Yamada, K. M. (2019). Durotaxis by Human Cancer Cells. Biophysical journal, 116(4), 670–683. https://doi.org/10.1016/j.bpj.2019.01.009
Gilkes, D. M., Semenza, G. L., & Wirtz, D. (2014). Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nature reviews. Cancer, 14(6), 430–439. https://doi.org/10.1038/nrc3726
Kalluri, R., & Weinberg, R. A. (2009). The basics of epithelial-mesenchymal transition. The Journal of clinical investigation, 119(6), 1420–1428. https://doi.org/10.1172/JCI39104
What are cell-matrix adhesions?. Mbi.nus.edu.sg. (n.d.). https://www.mbi.nus.edu.sg/mbinfo/what-are-cell-matrix-adhesions/
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