Evidence map›Paper›PMID 34599101›Full record

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

Nanoconfinement of microvilli alters gene expression and boosts T cell activation.

Morteza Aramesh, Diana Stoycheva, Ioana Sandu, Stephan J Ihle, Tamara Zünd, Jau-Ye Shiu, Csaba Forró, Mohammad Asghari, Margherita Bernero, Sebastian Lickert and 3 more

Erratum issuedOpen access · greenAbstract 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. An erratum has been issued. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.0field-weighted citation impact, top 7% of its field
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

29 citing papers in PubMed, 51 citations in OpenAlex.

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  13. The physical landscape of CAR-T synapse.Biophysical journal · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 6 countries.

Morteza ArameshLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland; morteza.aramesh@hest.ethz.ch enrico.klotzsch@hest.ethz.ch.ORCID 0000-0003-2071-1929
Diana StoychevaLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland.
Ioana SanduInstitute of Microbiology, Department of Biology, ETH Zürich, Zürich, 8093, Switzerland.
Stephan J IhleLaboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, ETH Zürich, Zürich, 8092, Switzerland.
Tamara ZündLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland.
Jau-Ye ShiuLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland.
Csaba ForróDepartment of Chemistry, Stanford University, Stanford, CA 94305.
Mohammad AsghariInstitute for Chemical and Bioengineering, Department of Chemistry and Applied Biosciences, ETH Zürich, Zürich, 8093, Switzerland.
Margherita BerneroLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland.
Sebastian LickertLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland.ORCID 0000-0002-0569-9362
Annette OxeniusInstitute of Microbiology, Department of Biology, ETH Zürich, Zürich, 8093, Switzerland.
Viola VogelLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland.ORCID 0000-0003-2898-7671
Enrico KlotzschLaboratory of Applied Mechanobiology, Department for Health Sciences and Technology, ETH Zürich, Zürich, 8093, Switzerland; morteza.aramesh@hest.ethz.ch enrico.klotzsch@hest.ethz.ch.
ETH Zurich · CHJohn Radcliffe Hospital · GBChina Medical University · TWItalian Institute of Technology · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanism by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200-nm pores but not in 400-nm pores. Consequently, formation of TCR nanoclustered hotspots within 200-nm pores allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.

Indexed as

ActinsAntigen-Presenting CellsCells, CulturedGene ExpressionHumansLymphocyte ActivationMicrovilliReceptors, Antigen, T-CellSignal TransductionT-LymphocytesActinsReceptors, Antigen, T-Cellcell-surface interactionsimmunoengineeringmechanobiologynanoconfinementT cell microvilli

Identifiers

PMID34599101
PMCPMC8501847
OpenAlexW3202733945

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.