Cargando…

DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions

The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signaling. The past decade has witnessed the development of molecular probes which have revealed many aspects...

Descripción completa

Detalles Bibliográficos
Autores principales: Hu, Yuesong, Duan, Yuxin, Velusamy, Arventh, Narum, Steven, Rogers, Jhordan, Salaita, Khalid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369911/
https://www.ncbi.nlm.nih.gov/pubmed/37503090
http://dx.doi.org/10.1101/2023.07.09.548279
_version_ 1785077858645835776
author Hu, Yuesong
Duan, Yuxin
Velusamy, Arventh
Narum, Steven
Rogers, Jhordan
Salaita, Khalid
author_facet Hu, Yuesong
Duan, Yuxin
Velusamy, Arventh
Narum, Steven
Rogers, Jhordan
Salaita, Khalid
author_sort Hu, Yuesong
collection PubMed
description The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signaling. The past decade has witnessed the development of molecular probes which have revealed many aspects of receptor mechanotransduction. However, most force probes are immobilized on hard substrates, thus failing to reveal mechanics in the physiological context of cell membranes. In this report, we developed DNA origami tension sensors (DOTS) which bear force sensors on a DNA origami breadboard and allow mapping of TCR mechanotransduction at dynamic intermembrane junctions. We demonstrate that TCR-antigen bonds experience 5–10 pN forces, and the mechanical events are dependent on cell state, antigen mobility, antigen potency, antigen height and F-actin activity. We tethered DOTS onto a microparticle to mechanically screen antigen in high throughput using flow cytometry. Finally, DOTS were anchored onto live B cell membranes thus producing the first quantification of TCR mechanics at authentic immune cell-cell junctions.
format Online
Article
Text
id pubmed-10369911
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Cold Spring Harbor Laboratory
record_format MEDLINE/PubMed
spelling pubmed-103699112023-07-27 DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions Hu, Yuesong Duan, Yuxin Velusamy, Arventh Narum, Steven Rogers, Jhordan Salaita, Khalid bioRxiv Article The T cell receptor (TCR) is thought to be a mechanosensor, meaning that it transmits mechanical force to its antigen and leverages the force to amplify the specificity and magnitude of TCR signaling. The past decade has witnessed the development of molecular probes which have revealed many aspects of receptor mechanotransduction. However, most force probes are immobilized on hard substrates, thus failing to reveal mechanics in the physiological context of cell membranes. In this report, we developed DNA origami tension sensors (DOTS) which bear force sensors on a DNA origami breadboard and allow mapping of TCR mechanotransduction at dynamic intermembrane junctions. We demonstrate that TCR-antigen bonds experience 5–10 pN forces, and the mechanical events are dependent on cell state, antigen mobility, antigen potency, antigen height and F-actin activity. We tethered DOTS onto a microparticle to mechanically screen antigen in high throughput using flow cytometry. Finally, DOTS were anchored onto live B cell membranes thus producing the first quantification of TCR mechanics at authentic immune cell-cell junctions. Cold Spring Harbor Laboratory 2023-07-12 /pmc/articles/PMC10369911/ /pubmed/37503090 http://dx.doi.org/10.1101/2023.07.09.548279 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Hu, Yuesong
Duan, Yuxin
Velusamy, Arventh
Narum, Steven
Rogers, Jhordan
Salaita, Khalid
DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions
title DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions
title_full DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions
title_fullStr DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions
title_full_unstemmed DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions
title_short DNA Origami Tension Sensors (DOTS) to study T cell receptor mechanics at membrane junctions
title_sort dna origami tension sensors (dots) to study t cell receptor mechanics at membrane junctions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10369911/
https://www.ncbi.nlm.nih.gov/pubmed/37503090
http://dx.doi.org/10.1101/2023.07.09.548279
work_keys_str_mv AT huyuesong dnaorigamitensionsensorsdotstostudytcellreceptormechanicsatmembranejunctions
AT duanyuxin dnaorigamitensionsensorsdotstostudytcellreceptormechanicsatmembranejunctions
AT velusamyarventh dnaorigamitensionsensorsdotstostudytcellreceptormechanicsatmembranejunctions
AT narumsteven dnaorigamitensionsensorsdotstostudytcellreceptormechanicsatmembranejunctions
AT rogersjhordan dnaorigamitensionsensorsdotstostudytcellreceptormechanicsatmembranejunctions
AT salaitakhalid dnaorigamitensionsensorsdotstostudytcellreceptormechanicsatmembranejunctions