Evidence map›Paper›PMID 34588308›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

DNA origami patterning of synthetic T cell receptors reveals spatial control of the sensitivity and kinetics of signal activation.

Rui Dong, Tural Aksel, Waipan Chan, Ronald N Germain, Ronald D Vale, Shawn M Douglas

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Analyzing Molecular Determinants of Nanodrugs' Cytotoxic Effects.International journal of molecular sciences · 2025
    Pooled it
  2. Programmable DNA Assemblies Reconstitute Supramolecular Protein Function.bioRxiv : the preprint server for biology · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. Clustering of Membrane Receptors: Insights from DNA Origami-Based Approaches.Small (Weinheim an der Bergstrasse, Germany) · 2025
    Review
  13. Proofreading and single-molecule sensitivity in T cell receptor signaling by condensate nucleation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. Article
  16. Review
  17. Design principles for accurate folding of DNA origami.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  18. Bottom-up synthetic immunology.Nature nanotechnology · 2024
    Review
  19. Article
  20. Fluidic Interface for Surface-based DNA Origami Studies.ACS applied materials & interfaces · 2024
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Rui DongDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143.ORCID 0000-0002-9118-3636
Tural AkselDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143.ORCID 0000-0002-8477-557X
Waipan ChanLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
Ronald N GermainLymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.ORCID 0000-0003-1495-9143
Ronald D ValeDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143; valer@hhmi.org shawn.douglas@gmail.com.
Shawn M DouglasDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143; valer@hhmi.org shawn.douglas@gmail.com.ORCID 0000-0001-5398-9041

Funding

DNA Nanotechnology platform for high-throughput cryo-EM studies of small proteinsF32GM119322 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AKSEL, TURAL · 2016 to 2017
$119k
NIGMS NIH HHS F32 GM119322
6 · The paper itself

Abstract

Receptor clustering plays a key role in triggering cellular activation, but the relationship between the spatial configuration of clusters and the elicitation of downstream intracellular signals remains poorly understood. We developed a DNA-origami-based system that is easily adaptable to other cellular systems and enables rich interrogation of responses to a variety of spatially defined inputs. Using a chimeric antigen receptor (CAR) T cell model system with relevance to cancer therapy, we studied signaling dynamics at single-cell resolution. We found that the spatial arrangement of receptors determines the ligand density threshold for triggering and encodes the temporal kinetics of signaling activities. We also showed that signaling sensitivity of a small cluster of high-affinity ligands is enhanced when surrounded by nonstimulating low-affinity ligands. Our results suggest that cells measure spatial arrangements of ligands, translate that information into distinct signaling dynamics, and provide insights into engineering immunotherapies.

Indexed as

AntigensCell Line, TumorDNAHumansImmunotherapyJurkat CellsKineticsLigandsLymphocyte ActivationReceptors, Antigen, T-CellReceptors, Chimeric AntigenSignal TransductionT-LymphocytesAntigensDNALigandsReceptors, Antigen, T-CellReceptors, Chimeric Antigenchimeric antigen receptor T cellDNA origamiimmunotherapyMAP kinase signalingT cell signaling

Identifiers

PMID34588308
PMCPMC8501782

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.