ArticleNature communications2024
Mechanical force regulates ligand binding and function of PD-1.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- SynNotch Receptors for Visualizing Immunoreceptor Force Transmission and Downstream Signaling In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SynNotch receptors for visualizing immunoreceptor force transmission and downstream signaling in vivo.bioRxiv : the preprint server for biology · 2026Article
- Mechanical force regulates the inhibitory function of PD-1.EMBO reports · 2026Article
- Engineering macrophages for cancer immunotherapy: emerging insights and therapeutic potential.npj biomedical innovations · 2026Review
- Mechanoimmunology: past, present, and future perspectives.Mechanobiology in medicine · 2026Review
- Mechanotransduction through T cell receptors: consensus, controversies and future outlooks.Experimental & molecular medicine · 2026Review
- Is there a link between fascia and cancer? From potential mechanisms to future treatment options.Frontiers in physiology · 2026Review
- Mechanomedicine: Present state and future promise.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cell deformability enhances adhesion of ATRA-differentiated HL-60 cells to P-selectin.European journal of medical research · 2025Article
- DNA Origami Tension Sensors (DOTS) for Single-Molecule Force Measurements at Fluid Intermembrane Junctions.Nano letters · 2025Article
- Mechanoregulation of lymphocyte cytotoxicity.Nature reviews. Immunology · 2025Review
- Mechanical interactions impact the functions of immune cells and their application in immunoengineering.Advanced therapeutics · 2025Article
- The physical landscape of CAR-T synapse.Biophysical journal · 2024Review
- Mechanical regulation of lymphocyte activation and function.Journal of cell science · 2024Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Despite the success of PD-1 blockade in cancer therapy, how PD-1 initiates signaling remains unclear. Soluble PD-L1 is found in patient sera and can bind PD-1 but fails to suppress T cell function. Here, we show that PD-1 function is reduced when mechanical support on ligand is removed. Mechanistically, cells exert forces to PD-1 and prolong bond lifetime at forces <7 pN (catch bond) while accelerate dissociation at forces >8pN (slip bond). Molecular dynamics of PD-1-PD-L2 complex suggests force may cause relative rotation and translation between the two molecules yielding distinct atomic contacts not observed in the crystal structure. Compared to wild-type, PD-1 mutants targeting the force-induced distinct interactions maintain the same binding affinity but suppressed/eliminated catch bond, lowered rupture force, and reduced inhibitory function. Our results uncover a mechanism for cells to probe the mechanical support of PD-1-PD-Ligand bonds using endogenous forces to regulate PD-1 signaling.
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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.