ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Substrate rigidity regulates human T cell activation and proliferation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers.
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Who cites it
191 citing papers in PubMed, 320 citations in OpenAlex.
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- Tunable Enhancement of T Cell Expansion Through Modulation of Stiffness and Adhesion Receptor Engagement in an Engineered Hydrogel Platform.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Physical cues influence the construction of the osteoimmune microenvironment: focus on the hematoma period.Regenerative biomaterials · 2026Review
- Collagen-mediated pro-tumorigenic MAPK activation drives stromal-immune reprogramming in solid cancers.Frontiers in immunology · 2026Article
- Mechanical properties of the tumor microenvironment: drivers of immunotherapy resistance in solid tumors.Frontiers in immunology · 2026Review
- Integrin-Mediated Mechanosensing of Modeled Lymph Node Microenvironment Promotes T Cell Activation via Nuclear Deformation.Research (Washington, D.C.) · 2026Article
- Predicting Mechanosensitive T Cell Expansion from Cell Spreading.Advanced healthcare materials · 2025Article
- Chimeric Antigen Receptors Transmit Co-stimulatory Domain Dependent Piconewton Forces to their Target.bioRxiv : the preprint server for biology · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Synthetic Biology and Biomaterials Strategies to Deceive the Tumor Microenvironment in CAR-T Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2025Review
- Impact of 3D cell culture hydrogels derived from basement membrane extracts or nanofibrillar cellulose on CAR-T cell activation.iScience · 2025Article
131 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Adoptive immunotherapy using cultured T cells holds promise for the treatment of cancer and infectious disease. Ligands immobilized on surfaces fabricated from hard materials such as polystyrene plastic are commonly employed for T cell culture. The mechanical properties of a culture surface can influence the adhesion, proliferation, and differentiation of stem cells and fibroblasts. We therefore explored the impact of culture substrate stiffness on the ex vivo activation and expansion of human T cells. We describe a simple system for the stimulation of the TCR/CD3 complex and the CD28 receptor using substrates with variable rigidity manufactured from poly(dimethylsiloxane), a biocompatible silicone elastomer. We show that softer (Young's Modulus [E] < 100 kPa) substrates stimulate an average 4-fold greater IL-2 production and ex vivo proliferation of human CD4(+) and CD8(+) T cells compared with stiffer substrates (E > 2 MPa). Mixed peripheral blood T cells cultured on the stiffer substrates also demonstrate a trend (nonsignificant) toward a greater proportion of CD62L(neg), effector-differentiated CD4(+) and CD8(+) T cells. Naive CD4(+) T cells expanded on softer substrates yield an average 3-fold greater proportion of IFN-γ-producing Th1-like cells. These results reveal that the rigidity of the substrate used to immobilize T cell stimulatory ligands is an important and previously unrecognized parameter influencing T cell activation, proliferation, and Th differentiation. Substrate rigidity should therefore be a consideration in the development of T cell culture systems as well as when interpreting results of T cell activation based upon solid-phase immobilization of TCR/CD3 and CD28 ligands.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.