ArticleProceedings of the National Academy of Sciences of the United States of America2016
DNA-based nanoparticle tension sensors reveal that T-cell receptors transmit defined pN forces to their antigens for enhanced fidelity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 208 papers.
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Who cites it
208 citing papers in PubMed, 336 citations in OpenAlex.
- Mechano-immunomodulatory biomaterials: From immune mechanosensing to translational design.Bioactive materials · 2026Review
- Imaging and Calibration of Receptor-Specific Cellular Forces Using Biotinylated Ligands.Angewandte Chemie (International ed. in English) · 2026Article
- Decoding mechanoregulation in immunological synapses using biomimetic artificial cells.Nature methods · 2026Article
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.Science advances · 2026Article
- SynNotch Receptors for Visualizing Immunoreceptor Force Transmission and Downstream Signaling In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LB-PaCS-MD Guided Simulations Reveal Transient Stabilization during TCR-pMHC Dissociation.Journal of chemical information and modeling · 2026Article
- SynNotch receptors for visualizing immunoreceptor force transmission and downstream signaling in vivo.bioRxiv : the preprint server for biology · 2026Article
- LFA-1 mechanical dose controls DNAM-1 signalling and perforin polarization in NK cells.RSC advances · 2026Article
- Mechanobiology of CAR-T cell therapy: regulatory mechanisms and strategies for enhanced antitumor immunity.Journal of translational medicine · 2026Review
- Increased Nur77 is disconnected from TCR affinity in insulin-specific Tregs.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Measuring cellular force using DNA-based tension probes: from ensemble to single-molecule studies.Nature protocols · 2026Review
- Mechanoimmunology: past, present, and future perspectives.Mechanobiology in medicine · 2026Review
- Mechanical communication and function regulation of immune cells.Fundamental research · 2026Review
- Mechano-regulation of cancer cell memory in tumor progression and therapy.Mechanobiology in medicine · 2026Review
- Guidance for 3D traction force microscopy today and in the next decade.Nature methods · 2026Review
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Review
- Antibody Fc receptor CD16a mediates natural killer cell activation via mechanotransduction of piconewton forces.bioRxiv : the preprint server for biology · 2026Article
- Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.NPJ systems biology and applications · 2026Article
- Evaluating the effects of CD8/CD4 on T cell function in terms of TCR-pMHC-coreceptor catch and slip bonds.Frontiers in immunology · 2026Article
148 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
T cells are triggered when the T-cell receptor (TCR) encounters its antigenic ligand, the peptide-major histocompatibility complex (pMHC), on the surface of antigen presenting cells (APCs). Because T cells are highly migratory and antigen recognition occurs at an intermembrane junction where the T cell physically contacts the APC, there are long-standing questions of whether T cells transmit defined forces to their TCR complex and whether chemomechanical coupling influences immune function. Here we develop DNA-based gold nanoparticle tension sensors to provide, to our knowledge, the first pN tension maps of individual TCR-pMHC complexes during T-cell activation. We show that naïve T cells harness cytoskeletal coupling to transmit 12-19 pN of force to their TCRs within seconds of ligand binding and preceding initial calcium signaling. CD8 coreceptor binding and lymphocyte-specific kinase signaling are required for antigen-mediated cell spreading and force generation. Lymphocyte function-associated antigen 1 (LFA-1) mediated adhesion modulates TCR-pMHC tension by intensifying its magnitude to values >19 pN and spatially reorganizes the location of TCR forces to the kinapse, the zone located at the trailing edge of migrating T cells, thus demonstrating chemomechanical crosstalk between TCR and LFA-1 receptor signaling. Finally, T cells display a dampened and poorly specific response to antigen agonists when TCR forces are chemically abolished or physically "filtered" to a level below ∼12 pN using mechanically labile DNA tethers. Therefore, we conclude that T cells tune TCR mechanics with pN resolution to create a checkpoint of agonist quality necessary for specific immune response.
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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.