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The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale

Cell-cell contacts often underpin signaling between cells. For immunology, the binding of a T cell receptor to an antigen-presenting pMHC initiates downstream signaling and an immune response. Although this contact is mediated by proteins on both cells creating interfaces with gap sizes typically ar...

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Autores principales: Kulenkampff, Klara, Lippert, Anna H., McColl, James, Santos, Ana Mafalda, Ponjavic, Aleks, Jenkins, Edward, Humphrey, Jane, Winkel, Alexander, Franze, Kristian, Lee, Steven F., Davis, Simon J., Klenerman, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091464/
https://www.ncbi.nlm.nih.gov/pubmed/32075748
http://dx.doi.org/10.1016/j.bpj.2020.01.019
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author Kulenkampff, Klara
Lippert, Anna H.
McColl, James
Santos, Ana Mafalda
Ponjavic, Aleks
Jenkins, Edward
Humphrey, Jane
Winkel, Alexander
Franze, Kristian
Lee, Steven F.
Davis, Simon J.
Klenerman, David
author_facet Kulenkampff, Klara
Lippert, Anna H.
McColl, James
Santos, Ana Mafalda
Ponjavic, Aleks
Jenkins, Edward
Humphrey, Jane
Winkel, Alexander
Franze, Kristian
Lee, Steven F.
Davis, Simon J.
Klenerman, David
author_sort Kulenkampff, Klara
collection PubMed
description Cell-cell contacts often underpin signaling between cells. For immunology, the binding of a T cell receptor to an antigen-presenting pMHC initiates downstream signaling and an immune response. Although this contact is mediated by proteins on both cells creating interfaces with gap sizes typically around 14 nm, many, often contradictory observations have been made regarding the influence of the contact on parameters such as the binding kinetics, spatial distribution, and diffusion of signaling proteins within the contact. Understanding the basic physical constraints on probes inside this crowded environment will help inform studies on binding kinetics and dynamics of signaling of relevant proteins in the synapse. By tracking quantum dots of different dimensions for extended periods of time, we have shown that it is possible to obtain the probability of a molecule entering the contact, the change in its diffusion upon entry, and the impact of spatial heterogeneity of adhesion protein density in the contact. By analyzing the contacts formed by a T cell interacting with adhesion proteins anchored to a supported lipid bilayer, we find that probes are excluded from contact entry in a size-dependent manner for gap-to-probe differences of 4.1 nm. We also observed probes being trapped inside the contact and a decrease in diffusion of up to 85% in dense adhesion protein contacts. This approach provides new, to our knowledge, insights into the nature of cell-cell contacts, revealing that cell contacts are highly heterogeneous because of topography- and protein-density-related processes. These effects are likely to profoundly influence signaling between cells.
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spelling pubmed-70914642020-10-10 The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale Kulenkampff, Klara Lippert, Anna H. McColl, James Santos, Ana Mafalda Ponjavic, Aleks Jenkins, Edward Humphrey, Jane Winkel, Alexander Franze, Kristian Lee, Steven F. Davis, Simon J. Klenerman, David Biophys J Articles Cell-cell contacts often underpin signaling between cells. For immunology, the binding of a T cell receptor to an antigen-presenting pMHC initiates downstream signaling and an immune response. Although this contact is mediated by proteins on both cells creating interfaces with gap sizes typically around 14 nm, many, often contradictory observations have been made regarding the influence of the contact on parameters such as the binding kinetics, spatial distribution, and diffusion of signaling proteins within the contact. Understanding the basic physical constraints on probes inside this crowded environment will help inform studies on binding kinetics and dynamics of signaling of relevant proteins in the synapse. By tracking quantum dots of different dimensions for extended periods of time, we have shown that it is possible to obtain the probability of a molecule entering the contact, the change in its diffusion upon entry, and the impact of spatial heterogeneity of adhesion protein density in the contact. By analyzing the contacts formed by a T cell interacting with adhesion proteins anchored to a supported lipid bilayer, we find that probes are excluded from contact entry in a size-dependent manner for gap-to-probe differences of 4.1 nm. We also observed probes being trapped inside the contact and a decrease in diffusion of up to 85% in dense adhesion protein contacts. This approach provides new, to our knowledge, insights into the nature of cell-cell contacts, revealing that cell contacts are highly heterogeneous because of topography- and protein-density-related processes. These effects are likely to profoundly influence signaling between cells. The Biophysical Society 2020-03-24 2020-01-28 /pmc/articles/PMC7091464/ /pubmed/32075748 http://dx.doi.org/10.1016/j.bpj.2020.01.019 Text en © 2020 Biophysical Society. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Articles
Kulenkampff, Klara
Lippert, Anna H.
McColl, James
Santos, Ana Mafalda
Ponjavic, Aleks
Jenkins, Edward
Humphrey, Jane
Winkel, Alexander
Franze, Kristian
Lee, Steven F.
Davis, Simon J.
Klenerman, David
The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale
title The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale
title_full The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale
title_fullStr The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale
title_full_unstemmed The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale
title_short The Costs of Close Contacts: Visualizing the Energy Landscape of Cell Contacts at the Nanoscale
title_sort costs of close contacts: visualizing the energy landscape of cell contacts at the nanoscale
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091464/
https://www.ncbi.nlm.nih.gov/pubmed/32075748
http://dx.doi.org/10.1016/j.bpj.2020.01.019
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