Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pullen, Robert H., Abel, Steven M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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
_version_ 1783449323438080000
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
work_keys_str_mv AT pullenroberth mechanicalfeedbackenablescatchbondstoselectivelystabilizescanningmicrovilliattcellsurfaces
AT abelstevenm mechanicalfeedbackenablescatchbondstoselectivelystabilizescanningmicrovilliattcellsurfaces