ArticleProceedings of the National Academy of Sciences of the United States of America2019
Biphasic mechanosensitivity of T cell receptor-mediated spreading of lymphocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
- Inference of the 3D pressure field exerted by a single cell from a thin membrane transverse deformation.The European physical journal. E, Soft matter · 2026Article
- 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
- Actin waves guide an outward movement of microclusters in the lymphocyte immunological synapse.EMBO reports · 2026Article
- Physical cues influence the construction of the osteoimmune microenvironment: focus on the hematoma period.Regenerative biomaterials · 2026Review
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Chemical compensation to mechanical loss in cell mechanosensation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Coupling Molecular and Cellular Dynamics in a Large-Scale Monte Carlo Simulation.International journal of molecular sciences · 2025Article
- Predicting Mechanosensitive T Cell Expansion from Cell Spreading.Advanced healthcare materials · 2025Article
- Platforms for studying cell-cell recognition by immune cells.Immunology and cell biology · 2025Review
- Mechanical interactions impact the functions of immune cells and their application in immunoengineering.Advanced therapeutics · 2025Article
- Antigen mobility regulates the dynamics and precision of antigen capture in the B cell immune synapse.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Piezo1 restrains proinflammatory response but is essential in T-cell-mediated immunopathology.Journal of leukocyte biology · 2025Article
- Focus on mechano-immunology: new direction in cancer treatment.International journal of surgery (London, England) · 2025Review
- Taming Variability in T-Cell Mechanosensing.Cells · 2025Article
- Insights into the mechanisms, regulation, and therapeutic implications of extracellular matrix stiffness in cancer.Bioengineering & translational medicine · 2025Review
- Article
- Quantifying T cell receptor mechanics at membrane junctions using DNA origami tension sensors.Nature nanotechnology · 2024Article
- Adaptive immunity of materials: Implications for tissue healing and regeneration.Bioactive materials · 2024Review
- Article
- Morphodynamics of T-lymphocytes: Scanning to spreading.Biophysical journal · 2024Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanosensing by T cells through the T cell receptor (TCR) is at the heart of immune recognition. While the mechanobiology of the TCR at the molecular level is increasingly well documented, its link to cell-scale response is poorly understood. Here we explore T cell spreading response as a function of substrate rigidity and show that remarkably, depending on the surface receptors stimulated, the cellular response may be either biphasic or monotonous. When adhering solely via the TCR complex, T cells respond to environmental stiffness in an unusual fashion, attaining maximal spreading on an optimal substrate stiffness comparable to that of professional antigen-presenting cells. However, in the presence of additional ligands for the integrin LFA-1, this biphasic response is abrogated and the cell spreading increases monotonously with stiffness up to a saturation value. This ligand-specific mechanosensing is effected through an actin-polymerization-dependent mechanism. We construct a mesoscale semianalytical model based on force-dependent bond rupture and show that cell-scale biphasic or monotonous behavior emerges from molecular parameters. As the substrate stiffness is increased, there is a competition between increasing effective stiffness of the bonds, which leads to increased cell spreading and increasing bond breakage, which leads to decreased spreading. We hypothesize that the link between actin and the receptors (TCR or LFA-1), rather than the ligand/receptor linkage, is the site of this mechanosensing.
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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.