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Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces
T-cells use microvilli to search the surfaces of antigen-presenting cells for antigenic ligands. The active motion of scanning microvilli provides a force-generating mechanism that is intriguing in light of single-molecule experiments showing that applied forces increase the lifetimes of stimulatory...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727777/ https://www.ncbi.nlm.nih.gov/pubmed/31116687 http://dx.doi.org/10.1091/mbc.E19-01-0048 |
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author | Pullen, Robert H. Abel, Steven M. |
author_facet | Pullen, Robert H. Abel, Steven M. |
author_sort | Pullen, Robert H. |
collection | PubMed |
description | T-cells use microvilli to search the surfaces of antigen-presenting cells for antigenic ligands. The active motion of scanning microvilli provides a force-generating mechanism that is intriguing in light of single-molecule experiments showing that applied forces increase the lifetimes of stimulatory receptor–ligand bonds (catch-bond behavior). In this work, we introduce a theoretical framework to explore the motion of a microvillar tip above an antigen-presenting surface when receptors on the tip stochastically bind to ligands on the surface and dissociate from them in a force-dependent manner. Forces on receptor-ligand bonds impact the motion of the microvillus, leading to feedback between binding and microvillar motion. We use computer simulations to show that the average microvillar velocity varies in a ligand-dependent manner; that catch bonds generate responses in which some microvilli almost completely stop, while others move with a broad distribution of velocities; and that the frequency of stopping depends on the concentration of stimulatory ligands. Typically, a small number of catch bonds initially immobilize the microvillus, after which additional bonds accumulate and increase the cumulative receptor-engagement time. Our results demonstrate that catch bonds can selectively slow and stabilize scanning microvilli, suggesting a physical mechanism that may contribute to antigen discrimination by T-cells. |
format | Online Article Text |
id | pubmed-6727777 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67277772019-10-07 Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces Pullen, Robert H. Abel, Steven M. Mol Biol Cell Articles T-cells use microvilli to search the surfaces of antigen-presenting cells for antigenic ligands. The active motion of scanning microvilli provides a force-generating mechanism that is intriguing in light of single-molecule experiments showing that applied forces increase the lifetimes of stimulatory receptor–ligand bonds (catch-bond behavior). In this work, we introduce a theoretical framework to explore the motion of a microvillar tip above an antigen-presenting surface when receptors on the tip stochastically bind to ligands on the surface and dissociate from them in a force-dependent manner. Forces on receptor-ligand bonds impact the motion of the microvillus, leading to feedback between binding and microvillar motion. We use computer simulations to show that the average microvillar velocity varies in a ligand-dependent manner; that catch bonds generate responses in which some microvilli almost completely stop, while others move with a broad distribution of velocities; and that the frequency of stopping depends on the concentration of stimulatory ligands. Typically, a small number of catch bonds initially immobilize the microvillus, after which additional bonds accumulate and increase the cumulative receptor-engagement time. Our results demonstrate that catch bonds can selectively slow and stabilize scanning microvilli, suggesting a physical mechanism that may contribute to antigen discrimination by T-cells. The American Society for Cell Biology 2019-07-22 /pmc/articles/PMC6727777/ /pubmed/31116687 http://dx.doi.org/10.1091/mbc.E19-01-0048 Text en © 2019 Pullen and Abel. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Pullen, Robert H. Abel, Steven M. Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces |
title | Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces |
title_full | Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces |
title_fullStr | Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces |
title_full_unstemmed | Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces |
title_short | Mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at T-cell surfaces |
title_sort | mechanical feedback enables catch bonds to selectively stabilize scanning microvilli at t-cell surfaces |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727777/ https://www.ncbi.nlm.nih.gov/pubmed/31116687 http://dx.doi.org/10.1091/mbc.E19-01-0048 |
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