{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:00:21Z","timestamp":1792803621248,"version":"4.5.0"},"reference-count":140,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T00:00:00Z","timestamp":1625011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovate UKRI Research Knowledge Transfer Partnership","award":["KTP: Self-assembling peptide matrices as a platform for cell biology studies and drug delivery"],"award-info":[{"award-number":["KTP: Self-assembling peptide matrices as a platform for cell biology studies and drug delivery"]}],"id":[{"id":"https:\/\/ror.org\/05ar5fy68","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The tumor microenvironment plays a critical role in modulating cancer cell migration, metabolism, and malignancy, thus, highlighting the need to develop in vitro culture systems that can recapitulate its abnormal properties. While a variety of stiffness-tunable biomaterials, reviewed here, have been developed to mimic the rigidity of the tumor extracellular matrix, culture systems that can recapitulate the broader extracellular context of the tumor microenvironment (including pH and temperature) remain comparably unexplored, partially due to the difficulty in independently tuning these parameters. Here, we investigate a self-assembled polypeptide network hydrogel as a cell culture platform and demonstrate that the culture parameters, including the substrate stiffness, extracellular pH and temperature, can be independently controlled. We then use this biomaterial as a cell culture substrate to assess the effect of stiffness, pH and temperature on Suit2 cells, a pancreatic cancer cell line, and demonstrate that these microenvironmental factors can regulate two critical transcription factors in cancer: yes-associated protein 1 (YAP) and hypoxia inducible factor (HIF-1A).<\/jats:p>","DOI":"10.3390\/cancers13133286","type":"journal-article","created":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T10:03:19Z","timestamp":1625047399000},"page":"3286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Self-Assembling Polypeptide Hydrogels as a Platform to Recapitulate the Tumor Microenvironment"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1194-8019","authenticated-orcid":false,"given":"Dariusz","family":"Lachowski","sequence":"first","affiliation":[{"name":"Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, South Kensington Campus, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3589-6252","authenticated-orcid":false,"given":"Carlos","family":"Matellan","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, South Kensington Campus, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-1323","authenticated-orcid":false,"given":"Ernesto","family":"Cortes","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, South Kensington Campus, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Saiani","sequence":"additional","affiliation":[{"name":"Department of Materials, Manchester Institute of Biotechnology, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline F.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering and Analytical Science, Manchester Institute of Biotechnology, Faculty of Science and Engineering, The University of Manchester, Oxford Road, Manchester M13 9PL, UK"},{"name":"Manchester BIOGEL, Mereside, Alderley Park, Alderley Edge, Cheshire SK10 4TG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-8910","authenticated-orcid":false,"given":"Armando E.","family":"del R\u00edo Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biomechanics Laboratory, Department of Bioengineering, Faculty of Engineering, South Kensington Campus, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"jcs229013","DOI":"10.1242\/jcs.229013","article-title":"Engineering the cellular mechanical microenvironment\u2014From bulk mechanics to the nanoscale","volume":"132","author":"Matellan","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_2","first-page":"2409","article-title":"Effect of fibroblast co-culture on the proliferation, viability and drug response of colon cancer cells","volume":"17","author":"Koh","year":"2018","journal-title":"Oncol. Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.yexcr.2015.05.016","article-title":"Co-culture of 3D tumor spheroids with fibroblasts as a model for epithelial\u2013mesenchymal transition in vitro","volume":"335","author":"Kim","year":"2015","journal-title":"Exp. Cell Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e2815","DOI":"10.21769\/BioProtoc.2815","article-title":"3D Co-culture System of Tumor-associated Macrophages and Ovarian Cancer Cells","volume":"8","author":"Long","year":"2018","journal-title":"Bio-Protocol"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.celrep.2018.12.090","article-title":"Modeling Tumor Phenotypes In Vitro with Three-Dimensional Bioprinting","volume":"26","author":"Langer","year":"2019","journal-title":"Cell Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Watters, K.M., Bajwa, P., and Kenny, H.A. (2018). Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment. Cancers, 10.","DOI":"10.3390\/cancers10080265"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.4161\/cbt.21353","article-title":"Cancer cell spheroids as a model to evaluate chemotherapy protocols","volume":"13","author":"Perche","year":"2012","journal-title":"Cancer Biol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41568-018-0007-6","article-title":"Organoids in cancer research","volume":"18","author":"Drost","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1039\/C8LC00596F","article-title":"Tumor-on-a-chip platform to investigate progression and drug sensitivity in cell lines and patient-derived organoids","volume":"18","author":"Shirure","year":"2018","journal-title":"Lab Chip"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kashaninejad, N., Nikmaneshi, M.R., Moghadas, H., Oskouei, A.K., Rismanian, M., Barisam, M., Saidi, M.S., and Firoozabadi, B. (2016). Organ-Tumor-on-a-Chip for Chemosensitivity Assay: A Critical Review. Micromachines, 7.","DOI":"10.3390\/mi7080130"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1002\/jcb.27681","article-title":"Extracellular matrix (ECM) stiffness and degradation as cancer drivers","volume":"120","author":"Najafi","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/s10585-019-09966-1","article-title":"The extracellular matrix in tumor progression and metastasis","volume":"36","author":"Eble","year":"2019","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12630","DOI":"10.1038\/ncomms12630","article-title":"ATRA mechanically reprograms pancreatic stellate cells to suppress matrix remodelling and inhibit cancer cell invasion","volume":"7","author":"Chronopoulos","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e352","DOI":"10.1038\/oncsis.2017.54","article-title":"Matrix stiffness induces epithelial\u2013mesenchymal transition and promotes chemoresistance in pancreatic cancer cells","volume":"6","author":"Rice","year":"2017","journal-title":"Oncogenesis"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yeldag, G., Rice, A., and Hern\u00e1ndez, A.D.R. (2018). Chemoresistance and the Self-Maintaining Tumor Microenvironment. Cancers, 10.","DOI":"10.3390\/cancers10120471"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1007\/s10555-019-09787-4","article-title":"Acidosis and cancer: From mechanism to neutralization","volume":"38","author":"Estrella","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3430","DOI":"10.7150\/jca.21125","article-title":"The Glycolytic Switch in Tumors: How Many Players Are Involved?","volume":"8","author":"Yu","year":"2017","journal-title":"J. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/nrc.2017.77","article-title":"Tumour acidosis: From the passenger to the driver\u2019s seat","volume":"17","author":"Corbet","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10555-019-09792-7","article-title":"Causes, consequences, and therapy of tumors acidosis","volume":"38","author":"Pillai","year":"2019","journal-title":"Cancer Metastasis Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: The metabolic requirements of cell proliferation","volume":"324","author":"Heiden","year":"2009","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nmeth.3839","article-title":"A practical guide to hydrogels for cell culture","volume":"13","author":"Caliari","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7913","DOI":"10.1016\/j.biomaterials.2011.07.005","article-title":"Elucidating the mechanobiology of malignant brain tumors using a brain matrix-mimetic hyaluronic acid hydrogel platform","volume":"32","author":"Ananthanarayanan","year":"2011","journal-title":"Biomaterials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.5582\/bst.2011.v5.1.10","article-title":"Invasion of carcinoma cells into reconstituted type I collagen gels: Visual real-time analysis by time-lapse microscopy","volume":"5","author":"Sakai","year":"2011","journal-title":"Biosci. Trends"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biomaterials.2019.02.018","article-title":"Identification of a mechanogenetic link between substrate stiffness and chemotherapeutic response in breast cancer","volume":"202","author":"Medina","year":"2019","journal-title":"Biomaterials"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/bit.25709","article-title":"Three-dimensional matrix stiffness and adhesive ligands affect cancer cell response to toxins","volume":"113","author":"Zustiak","year":"2015","journal-title":"Biotechnol. Bioeng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1163\/1568562042459698","article-title":"Effect of collagen gel stiffness on neurite extension","volume":"15","author":"Willits","year":"2004","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1016\/j.actbio.2012.08.007","article-title":"Tuning three-dimensional collagen matrix stiffness independently of collagen concentration modulates endothelial cell behavior","volume":"9","author":"Mason","year":"2013","journal-title":"Acta Biomater."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.bpj.2015.02.022","article-title":"The Effect of Substrate Stiffness, Thickness, and Cross-Linking Density on Osteogenic Cell Behavior","volume":"108","author":"Mullen","year":"2015","journal-title":"Biophys. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jmbbm.2013.06.013","article-title":"Osteocyte differentiation is regulated by extracellular matrix stiffness and intercellular separation","volume":"28","author":"Mullen","year":"2013","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.matlet.2012.01.036","article-title":"Riboflavin and collagen: New crosslinking methods to tailor the stiffness of hydrogels","volume":"74","author":"Tirella","year":"2012","journal-title":"Mater. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S0142-9612(00)00201-5","article-title":"Ionically crosslinked alginate hydrogels as scaffolds for tissue engineering: Part Structure, gelation rate and mechanical properties","volume":"22","author":"Kuo","year":"2001","journal-title":"Biomaterials"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.jmbbm.2014.04.013","article-title":"Mechanical properties of alginate hydrogels manufactured using external gelation","volume":"36","author":"Kaklamani","year":"2014","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/1754-1611-7-9","article-title":"Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness","volume":"7","author":"Candiello","year":"2013","journal-title":"J. Biol. Eng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1021\/bm049508a","article-title":"Controlled Degradation and Mechanical Behavior of Photopolymerized Hyaluronic Acid Networks","volume":"6","author":"Burdick","year":"2004","journal-title":"Biomacromolecules"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4881","DOI":"10.1016\/j.biomaterials.2006.05.012","article-title":"The use of poly(ethylene glycol) hydrogels to investigate the impact of ECM chemistry and mechanics on smooth muscle cells","volume":"27","author":"Peyton","year":"2006","journal-title":"Biomaterials"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1021\/acsami.8b18302","article-title":"Mechanical Properties and Concentrations of Poly(ethylene glycol) in Hydrogels and Brushes Direct the Surface Transport of Staphylococcus aureus","volume":"11","author":"Kolewe","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"21893","DOI":"10.1021\/acsami.5b09344","article-title":"Tuning the Range of Polyacrylamide Gel Stiffness for Mechanobiology Applications","volume":"8","author":"Denisin","year":"2016","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Palchesko, R.N., Zhang, L., Sun, Y., and Feinberg, A.W. (2012). Development of Polydimethylsiloxane Substrates with Tunable Elastic Modulus to Study Cell Mechanobiology in Muscle and Nerve. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051499"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/ncb2370","article-title":"Fibroblast polarization is a matrix-rigidity-dependent process controlled by focal adhesion mechanosensing","volume":"13","author":"Lichtenstein","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41563-019-0507-0","article-title":"Stopping transformed cancer cell growth by rigidity sensing","volume":"19","author":"Yang","year":"2020","journal-title":"Nat. Mater."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/jbm.a.36568","article-title":"Tuning of hydrogel stiffness using a two-component peptide system for mammalian cell culture","volume":"107","author":"Scelsi","year":"2019","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hiew, S.H., Mohanram, H., Ning, L., Guo, J., S\u00e1nchez-Ferrer, A., Shi, X., Pervushin, K., Mu, Y., Mezzenga, R., and Miserez, A. (2019). A Short Peptide Hydrogel with High Stiffness Induced by 3 10 -Helices to \u03b2-Sheet Transition in Water. Adv. Sci., 6.","DOI":"10.1002\/advs.201901173"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.matbio.2019.06.009","article-title":"Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro","volume":"85-86","author":"Ashworth","year":"2020","journal-title":"Matrix Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1016\/j.matchar.2010.05.010","article-title":"Development of collagen condensation method to improve mechanical strength of tissue engineering scaffolds","volume":"61","author":"Yunoki","year":"2010","journal-title":"Mater. Charact."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10.20.1","DOI":"10.1002\/cpcb.9","article-title":"Generation of 3D Collagen Gels with Controlled Diverse Architectures","volume":"72","author":"Doyle","year":"2016","journal-title":"Curr. Protoc. Cell Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1016\/j.biomaterials.2009.05.043","article-title":"Control of 3-dimensional collagen matrix polymerization for reproducible human mammary fibroblast cell culture in microfluidic devices","volume":"30","author":"Sung","year":"2009","journal-title":"Biomaterials"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.jmb.2007.12.047","article-title":"Fibrillogenesis in Dense Collagen Solutions: A Physicochemical Study","volume":"376","author":"Gobeaux","year":"2008","journal-title":"J. Mol. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1089\/ten.teb.2014.0086","article-title":"Review of collagen I hydrogels for bioengineered tissue microenvironments: Characterization of mechanics, structure, and transport","volume":"20","author":"Antoine","year":"2014","journal-title":"Tissue Eng. Part B Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.arabjc.2013.11.027","article-title":"Synthesis, characterization and rheological behavior of pH sensitive poly(acrylamide-co-acrylic acid) hydrogels","volume":"10","author":"Nesrinne","year":"2017","journal-title":"Arab. J. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1007\/s10856-010-4134-1","article-title":"Preparation and characterization of hybrid pH-sensitive hydrogels of chitosan-co-acrylic acid for controlled release of verapamil","volume":"21","author":"Ranjha","year":"2010","journal-title":"J. Mater. Sci. Mater. Electron."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7373","DOI":"10.1039\/C7CC01826F","article-title":"Effect of pH on chitosan hydrogel polymer network structure","volume":"53","author":"Xu","year":"2017","journal-title":"Chem. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.3390\/ma3031863","article-title":"Collagen-Based Biomaterials for Tissue Engineering Applications","volume":"3","author":"Gauvin","year":"2010","journal-title":"Materials"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1529\/biophysj.106.097998","article-title":"Noninvasive Assessment of Collagen Gel Microstructure and Mechanics Using Multiphoton Microscopy","volume":"92","author":"Raub","year":"2007","journal-title":"Biophys. J."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/pi.5149","article-title":"Biopolymeric nanocomposites for potential biomedical applications","volume":"65","author":"Sionkowska","year":"2016","journal-title":"Polym. Int."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1002\/jbm.a.32869","article-title":"Genipin-cross-linked collagen\/chitosan biomimetic scaffolds for articular cartilage tissue engineering applications","volume":"95","author":"Yan","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/pat.3842","article-title":"The review of versatile application of collagen","volume":"28","author":"Sionkowska","year":"2017","journal-title":"Polym. Adv. Technol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s10856-016-5763-9","article-title":"Evaluation of cell binding to collagen and gelatin: A study of the effect of 2D and 3D architecture and surface chemistry","volume":"27","author":"Davidenko","year":"2016","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1016\/j.bbamcr.2008.10.012","article-title":"Cell response to matrix mechanics: Focus on collagen","volume":"1793","author":"Plant","year":"2009","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1242\/bio.017632","article-title":"Quantitative analysis of 3D extracellular matrix remodelling by pancreatic stellate cells","volume":"5","author":"Robinson","year":"2016","journal-title":"Biol. Open"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.progpolymsci.2011.06.003","article-title":"Alginate: Properties and biomedical applications","volume":"37","author":"Lee","year":"2012","journal-title":"Prog. Polym. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1002\/mabi.200600069","article-title":"Alginate Hydrogels as Biomaterials","volume":"6","author":"Augst","year":"2006","journal-title":"Macromol. Biosci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.abb.2003.11.023","article-title":"Effect of substrate mechanics on chondrocyte adhesion to modified alginate surfaces","volume":"422","author":"Genes","year":"2004","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6239","DOI":"10.1016\/S0032-3861(02)00559-1","article-title":"Decoupling the dependence of rheological\/mechanical properties of hydrogels from solids con-centration","volume":"43","author":"Kong","year":"2002","journal-title":"Polymer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-17286-1","article-title":"Tuning Alginate Bioink Stiffness and Composition for Controlled Growth Factor Delivery and to Spatially Direct MSC Fate within Bioprinted Tissues","volume":"7","author":"Freeman","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.1021\/ma990514m","article-title":"Rigidity of Two-Component Hydrogels Prepared from Alginate and Poly(ethylene glycol)\u2212Diamines","volume":"32","author":"Eiselt","year":"1999","journal-title":"Macromolecules"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7852","DOI":"10.1039\/C9SM01039D","article-title":"Rheological properties and failure of alginate hydrogels with ionic and covalent crosslinks","volume":"15","author":"Hashemnejad","year":"2019","journal-title":"Soft Matter"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.actbio.2017.10.046","article-title":"Synthesis and evaluation of dual crosslinked alginate microbeads","volume":"65","author":"Somo","year":"2018","journal-title":"Acta Biomater."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.actbio.2017.08.041","article-title":"Hydrogel substrate stress-relaxation regulates the spreading and proliferation of mouse myoblasts","volume":"62","author":"Bauer","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/nmat2732","article-title":"Harnessing traction-mediated manipulation of the cell\/matrix interface to control stem-cell fate","volume":"9","author":"Huebsch","year":"2010","journal-title":"Nat. Mater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"H41","DOI":"10.1002\/adma.201003963","article-title":"Hyaluronic acid hydrogels for biomedical applications","volume":"23","author":"Burdick","year":"2011","journal-title":"Adv. Mater."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Khunmanee, S., Jeong, Y., and Park, H. (2017). Crosslinking method of hyaluronic-based hydrogel for biomedical applications. J. Tissue Eng., 8.","DOI":"10.1177\/2041731417726464"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1016\/j.biomaterials.2010.10.020","article-title":"Hydrogels with time-dependent material properties enhance cardiomyocyte differentiation in vitro","volume":"32","author":"Young","year":"2011","journal-title":"Biomaterials"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1016\/j.actbio.2009.12.024","article-title":"Synthesis and characterization of hyaluronic acid\u2013poly(ethylene glycol) hydrogels via Michael addition: An injectable biomaterial for cartilage repair","volume":"6","author":"Jin","year":"2010","journal-title":"Acta Biomater."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1039\/C6IB00027D","article-title":"Gradually softening hydrogels for modeling hepatic stellate cell behavior during fibrosis regression","volume":"8","author":"Caliari","year":"2016","journal-title":"Integr. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.reactfunctpolym.2018.06.010","article-title":"In situ-forming hyaluronic acid hydrogel through visible light-induced thiol-ene reaction","volume":"131","author":"Lee","year":"2018","journal-title":"React. Funct. Polym."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1038\/ncomms1792","article-title":"Stiffening hydrogels to probe short- and long-term cellular responses to dynamic mechanics","volume":"3","author":"Guvendiren","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/nmat3586","article-title":"Degradation-mediated cellular traction directs stem cell fate in covalently crosslinked three-dimensional hydrogels","volume":"12","author":"Khetan","year":"2013","journal-title":"Nat. Mater."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"21387","DOI":"10.1038\/srep21387","article-title":"Stiffening hydrogels for investigating the dynamics of hepatic stellate cell mechanotransduction during myofibroblast activation","volume":"6","author":"Caliari","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.actbio.2013.12.019","article-title":"Hyaluronan: A simple polysaccharide with diverse biological functions","volume":"10","author":"Dicker","year":"2014","journal-title":"Acta Biomater."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jmbbm.2013.11.008","article-title":"Hydrogels with differential and patterned mechanics to study stiffness-mediated myofibroblastic differentiation of hepatic stellate cells","volume":"38","author":"Guvendiren","year":"2014","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4639","DOI":"10.1016\/j.biomaterials.2010.02.044","article-title":"Bioactive modification of poly(ethylene glycol) hydrogels for tissue engineering","volume":"31","author":"Zhu","year":"2010","journal-title":"Biomaterials"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"667","DOI":"10.3389\/fchem.2018.00667","article-title":"Micro-Patterning of PEG-Based Hydrogels with Gold Nanoparticles Using a Reactive Micro-Contact-Printing Approach","volume":"6","author":"Yesildag","year":"2019","journal-title":"Front. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"40878","DOI":"10.1039\/C6RA08852J","article-title":"An alternative technique for patterning cells on poly(ethylene glycol) diacrylate hydrogels","volume":"6","author":"Peter","year":"2016","journal-title":"RSC Adv."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1039\/C3BM60278H","article-title":"Biomaterial arrays with defined adhesion ligand densities and matrix stiffness identify distinct phenotypes for tumorigenic and non-tumorigenic human mesenchymal cell types","volume":"2","author":"Hansen","year":"2014","journal-title":"Biomater. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1021\/bm049607o","article-title":"Network Formation and Degradation Behavior of Hydrogels Formed by Michael-Type Addition Reactions","volume":"6","author":"Metters","year":"2005","journal-title":"Biomacromolecules"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1002\/adma.200901808","article-title":"A Versatile Synthetic Extracellular Matrix Mimic via Thiol-Norbornene Photopolymerization","volume":"21","author":"Fairbanks","year":"2009","journal-title":"Adv. Mater."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/mame.201200119","article-title":"Characterization of Thiol-Ene Crosslinked PEG Hydrogels","volume":"298","author":"Toepke","year":"2013","journal-title":"Macromol. Mater. Eng."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4307","DOI":"10.1016\/S0142-9612(02)00175-8","article-title":"Photopolymerizable hydrogels for tissue engineering applications","volume":"23","author":"Nguyen","year":"2002","journal-title":"Biomaterials"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1126\/science.1169494","article-title":"Photodegradable Hydrogels for Dynamic Tuning of Physical and Chemical Properties","volume":"324","author":"Kloxin","year":"2009","journal-title":"Science"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.actbio.2016.10.027","article-title":"Enzyme-mediated stiffening hydrogels for probing activation of pancreatic stellate cells","volume":"48","author":"Liu","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"9912","DOI":"10.1002\/anie.201901989","article-title":"PEG\u2013Anthracene Hydrogels as an On-Demand Stiffening Matrix to Study Mechanobiology","volume":"58","author":"Ceccato","year":"2019","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1021\/bm501710e","article-title":"Photoresponsive Elastic Properties of Azobenzene-Containing Poly(ethylene-glycol)-Based Hydrogels","volume":"16","author":"Rosales","year":"2015","journal-title":"Biomacromolecules"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jconrel.2018.08.002","article-title":"Degradable poly(ethylene glycol) (PEG)-based hydrogels for spatiotemporal control of siR-NA\/nanoparticle delivery","volume":"287","author":"Wang","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1016\/S0032-3861(99)00629-1","article-title":"Fundamental studies of a novel, biodegradable PEG-b-PLA hydrogel","volume":"41","author":"Metters","year":"2000","journal-title":"Polymer"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1021\/bm0703564","article-title":"Synthesis and Characterization of Novel Thiol-Reactive Poly(ethylene glycol) Cross-Linkers for Extracellular-Matrix-Mimetic Biomaterials","volume":"8","author":"Vanderhooft","year":"2007","journal-title":"Biomacromolecules"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"7630","DOI":"10.1039\/c2sm25835h","article-title":"Microcontact printing of polyelectrolytes on PEG using an unmodified PDMS stamp for micropatterning nanoparticles, DNA, proteins and cells","volume":"8","author":"Wang","year":"2012","journal-title":"Soft Matter"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/S0142-9612(99)00224-0","article-title":"Surface modification using silanated poly(ethylene glycol)s","volume":"21","author":"Jo","year":"2000","journal-title":"Biomaterials"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.snb.2013.07.037","article-title":"Micropatterning of single cell arrays using the PEG-Silane and Biotin\u2013(Strept)Avidin System with photolithography and chemical vapor deposition","volume":"188","author":"Ren","year":"2013","journal-title":"Sens. Actuators B Chem."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Kumai, J., Sasagawa, S., Horie, M., and Yui, Y. (2021). A Novel Method for Polyacrylamide Gel Preparation Using N-hydroxysuccinimide-acrylamide Ester to Study Cell-Extracellular Matrix Mechanical Interactions. Front. Mater., 8.","DOI":"10.3389\/fmats.2021.637278"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"847","DOI":"10.2144\/000112026","article-title":"Bulk and micropatterned conjugation of extracellular matrix proteins to characterized polyacrylamide substrates for cell mechanotransduction assays","volume":"39","author":"Lagerholm","year":"2005","journal-title":"Biotechniques"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0091-679X(07)83002-0","article-title":"Polyacrylamide Hydrogels for Cell Mechanics: Steps Toward Optimization and Alternative Uses","volume":"83","author":"Kandow","year":"2007","journal-title":"Methods Cell Biol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"C1037","DOI":"10.1152\/ajpcell.67.2008","article-title":"Directing osteogenic and myogenic differentiation of MSCs: Interplay of stiffness and adhesive ligand presentation","volume":"295","author":"Rowlands","year":"2008","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1089\/ten.tea.2009.0614","article-title":"Effect of Matrix Elasticity on the Maintenance of the Chondrogenic Phenotype","volume":"16","author":"Schuh","year":"2010","journal-title":"Tissue Eng. Part A"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1002\/hep.24108","article-title":"Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells","volume":"53","author":"Schrader","year":"2011","journal-title":"Hepatology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/jbm.a.32951","article-title":"Stiffness of the substrate influences the phenotype of embryonic chicken cardiac myocytes","volume":"95","author":"Bajaj","year":"2010","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1016\/j.cell.2006.06.044","article-title":"Matrix Elasticity Directs Stem Cell Lineage Specification","volume":"126","author":"Engler","year":"2006","journal-title":"Cell"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-02689-x","article-title":"Substrate Rigidity Controls Activation and Durotaxis in Pancreatic Stellate Cells","volume":"7","author":"Lachowski","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"11190","DOI":"10.1073\/pnas.1611324113","article-title":"Vascular smooth muscle cell durotaxis depends on extracellular matrix composition","volume":"113","author":"Hartman","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"191796","DOI":"10.1098\/rsos.191796","article-title":"Influence of polydimethylsiloxane substrate stiffness on corneal epithelial cells","volume":"6","author":"Masterton","year":"2019","journal-title":"R. Soc. Open Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jmbbm.2014.09.020","article-title":"PDMS substrate stiffness affects the morphology and growth profiles of cancerous prostate and melanoma cells","volume":"41","author":"Raczkowska","year":"2015","journal-title":"J. Mech. Behav. Biomed. Mater."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"110995","DOI":"10.1016\/j.colsurfb.2020.110995","article-title":"Surface modifications to polydimethylsiloxane substrate for stabilizing prolonged bone marrow stromal cell culture","volume":"191","author":"Chuah","year":"2020","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.actbio.2015.05.023","article-title":"Combinatorial effect of substratum properties on mesenchymal stem cell sheet engineering and subsequent multi-lineage differentiation","volume":"23","author":"Chuah","year":"2015","journal-title":"Acta Biomater."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.biomaterials.2016.02.041","article-title":"Matrix stiffness modulates formation and activity of neuronal networks of controlled architectures","volume":"89","author":"Lantoine","year":"2016","journal-title":"Biomaterials"},{"key":"ref_114","first-page":"srep06215","article-title":"Stiff substrates enhance cultured neuronal network activity","volume":"4","author":"Zhang","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"25529","DOI":"10.1021\/acsami.5b09032","article-title":"EnhancedIn VitroBiocompatibility of Chemically Modified Poly(dimethylsiloxane) Surfaces for Stable Adhesion and Long-term Investigation of Brain Cerebral Cortex Cells","volume":"7","author":"Kuddannaya","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"9777","DOI":"10.1021\/am402903e","article-title":"Surface Chemical Modification of Poly(dimethylsiloxane) for the Enhanced Adhesion and Proliferation of Mesenchymal Stem Cells","volume":"5","author":"Kuddannaya","year":"2013","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1039\/C4BM00268G","article-title":"The effects of poly(dimethylsiloxane) surface silanization on the mesenchymal stem cell fate","volume":"3","author":"Chuah","year":"2014","journal-title":"Biomater. Sci."},{"key":"ref_118","first-page":"120","article-title":"Self-assemble peptide biomaterials and their biomedical applications","volume":"4","author":"Chen","year":"2019","journal-title":"Bioact. Mater."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1039\/C4RA13266A","article-title":"Tuning the mechanical and morphological properties of self-assembled peptide hydrogels via control over the gelation mechanism through regulation of ionic strength and the rate of pH change","volume":"5","author":"Li","year":"2014","journal-title":"RSC Adv."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1021\/acs.biomac.6b01693","article-title":"Controlling Self-Assembling Peptide Hydrogel Properties through Network Topology","volume":"18","author":"Gao","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"111539","DOI":"10.1016\/j.msec.2020.111539","article-title":"Functionalised peptide hydrogel for the delivery of cardiac progenitor cells","volume":"119","author":"Burgess","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8227","DOI":"10.7150\/thno.44276","article-title":"Self-assembling peptide hydrogels functionalized with LN- and BDNF- mimicking epitopes synergistically enhance peripheral nerve regeneration","volume":"10","author":"Yang","year":"2020","journal-title":"Theranostics"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"17076","DOI":"10.1021\/acsami.5b03605","article-title":"BMP7-Based Functionalized Self-Assembling Peptides for Nucleus Pulposus Tissue Engineering","volume":"7","author":"Tao","year":"2015","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"3334","DOI":"10.1073\/pnas.90.8.3334","article-title":"Spontaneous assembly of a self-complementary oligopeptide to form a stable macroscopic membrane","volume":"90","author":"Zhang","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"112200","DOI":"10.1016\/j.msec.2021.112200","article-title":"Neutrally charged self-assembling peptide hydrogel recapitulates in vitro mechanisms of breast cancer progression","volume":"127","author":"Clough","year":"2021","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1021\/acs.biomac.0c00229","article-title":"Role of Sheet-Edge Interactions in \u03b2-sheet Self-Assembling Peptide Hydrogels","volume":"21","author":"Wychowaniec","year":"2020","journal-title":"Biomacromolecules"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fonc.2018.00055","article-title":"Defining the Role of Solid Stress and Matrix Stiffness in Cancer Cell Proliferation and Metastasis","volume":"8","author":"Kalli","year":"2018","journal-title":"Front. Oncol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nrc.2016.73","article-title":"The biology and function of fibroblasts in cancer","volume":"16","author":"Kalluri","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.surg.2012.02.011","article-title":"Ki-67 predicts disease recurrence and poor prognosis in pancreatic neuroendocrine neoplasms","volume":"152","author":"Hamilton","year":"2012","journal-title":"Surgery"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1136\/jclinpath-2015-202985","article-title":"High Ki67 expression is an independent good prognostic marker in colorectal cancer","volume":"69","author":"Melling","year":"2016","journal-title":"J. Clin. Pathol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"747","DOI":"10.3892\/etm.2010.133","article-title":"Ki-67 as a prognostic marker according to breast cancer subtype and a predictor of recurrence time in primary breast cancer","volume":"1","author":"Nishimura","year":"2010","journal-title":"Exp. Ther. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"496","DOI":"10.20892\/j.issn.2095-3941.2016.0066","article-title":"Ki-67 as a prognostic marker according to breast cancer molecular subtype","volume":"13","author":"Soliman","year":"2016","journal-title":"Cancer Biol. Med."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1158\/0008-5472.CAN-12-2796","article-title":"Acidity Generated by the Tumor Microenvironment Drives Local Invasion","volume":"73","author":"Estrella","year":"2013","journal-title":"Cancer Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1096\/fj.09-149518","article-title":"NHE1 promotes invadopodial ECM proteolysis through acidification of the peri-invadopodial space","volume":"24","author":"Busco","year":"2010","journal-title":"FASEB J."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1007\/BF00121214","article-title":"Acidic pH enhances the invasive behavior of human melanoma cells","volume":"14","author":"Seftor","year":"1996","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"46557","DOI":"10.15252\/embr.201846557","article-title":"Tamoxifen mechanically reprograms the tumor microenvironment via HIF-1A and reduces cancer cell survival","volume":"20","author":"Cortes","year":"2019","journal-title":"EMBO Rep."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1161\/ATVBAHA.117.309249","article-title":"Mechanical Activation of Hypoxia-Inducible Factor 1\u03b1 Drives Endothelial Dysfunction at Atheroprone Sites","volume":"37","author":"Feng","year":"2017","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1161\/hh0202.104923","article-title":"Early Expression of Myocardial HIF-1\u03b1 in Response to Mechanical Stresses","volume":"90","author":"Kim","year":"2002","journal-title":"Circ. Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/nmat4051","article-title":"Interplay of matrix stiffness and protein tethering in stem cell differentiation","volume":"13","author":"Wen","year":"2014","journal-title":"Nat. Mater."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/13\/3286\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:23:59Z","timestamp":1760163839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/13\/13\/3286"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,30]]},"references-count":140,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["cancers13133286"],"URL":"https:\/\/doi.org\/10.3390\/cancers13133286","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,30]]}}}