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Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales
Cellular sorting and pattern formation are crucial for many biological processes such as development, tissue regeneration, and cancer progression. Prominent physical driving forces for cellular sorting are differential adhesion and contractility. Here, we studied the segregation of epithelial cocult...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104523/ https://www.ncbi.nlm.nih.gov/pubmed/37011207 http://dx.doi.org/10.1073/pnas.2213186120 |
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author | Skamrahl, Mark Schünemann, Justus Mukenhirn, Markus Pang, Hongtao Gottwald, Jannis Jipp, Marcel Ferle, Maximilian Rübeling, Angela Oswald, Tabea A. Honigmann, Alf Janshoff , Andreas |
author_facet | Skamrahl, Mark Schünemann, Justus Mukenhirn, Markus Pang, Hongtao Gottwald, Jannis Jipp, Marcel Ferle, Maximilian Rübeling, Angela Oswald, Tabea A. Honigmann, Alf Janshoff , Andreas |
author_sort | Skamrahl, Mark |
collection | PubMed |
description | Cellular sorting and pattern formation are crucial for many biological processes such as development, tissue regeneration, and cancer progression. Prominent physical driving forces for cellular sorting are differential adhesion and contractility. Here, we studied the segregation of epithelial cocultures containing highly contractile, ZO1/2-depleted MDCKII cells (dKD) and their wild-type (WT) counterparts using multiple quantitative, high-throughput methods to monitor their dynamical and mechanical properties. We observe a time-dependent segregation process governed mainly by differential contractility on short (<5 h) and differential adhesion on long (>5 h) timescales. The overly contractile dKD cells exert strong lateral forces on their WT neighbors, thereby apically depleting their surface area. Concomitantly, the tight junction–depleted, contractile cells exhibit weaker cell–cell adhesion and lower traction force. Drug-induced contractility reduction and partial calcium depletion delay the initial segregation but cease to change the final demixed state, rendering differential adhesion the dominant segregation force at longer timescales. This well-controlled model system shows how cell sorting is accomplished through a complex interplay between differential adhesion and contractility and can be explained largely by generic physical driving forces. |
format | Online Article Text |
id | pubmed-10104523 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-101045232023-10-03 Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales Skamrahl, Mark Schünemann, Justus Mukenhirn, Markus Pang, Hongtao Gottwald, Jannis Jipp, Marcel Ferle, Maximilian Rübeling, Angela Oswald, Tabea A. Honigmann, Alf Janshoff , Andreas Proc Natl Acad Sci U S A Physical Sciences Cellular sorting and pattern formation are crucial for many biological processes such as development, tissue regeneration, and cancer progression. Prominent physical driving forces for cellular sorting are differential adhesion and contractility. Here, we studied the segregation of epithelial cocultures containing highly contractile, ZO1/2-depleted MDCKII cells (dKD) and their wild-type (WT) counterparts using multiple quantitative, high-throughput methods to monitor their dynamical and mechanical properties. We observe a time-dependent segregation process governed mainly by differential contractility on short (<5 h) and differential adhesion on long (>5 h) timescales. The overly contractile dKD cells exert strong lateral forces on their WT neighbors, thereby apically depleting their surface area. Concomitantly, the tight junction–depleted, contractile cells exhibit weaker cell–cell adhesion and lower traction force. Drug-induced contractility reduction and partial calcium depletion delay the initial segregation but cease to change the final demixed state, rendering differential adhesion the dominant segregation force at longer timescales. This well-controlled model system shows how cell sorting is accomplished through a complex interplay between differential adhesion and contractility and can be explained largely by generic physical driving forces. National Academy of Sciences 2023-04-03 2023-04-11 /pmc/articles/PMC10104523/ /pubmed/37011207 http://dx.doi.org/10.1073/pnas.2213186120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Physical Sciences Skamrahl, Mark Schünemann, Justus Mukenhirn, Markus Pang, Hongtao Gottwald, Jannis Jipp, Marcel Ferle, Maximilian Rübeling, Angela Oswald, Tabea A. Honigmann, Alf Janshoff , Andreas Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
title | Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
title_full | Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
title_fullStr | Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
title_full_unstemmed | Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
title_short | Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
title_sort | cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales |
topic | Physical Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104523/ https://www.ncbi.nlm.nih.gov/pubmed/37011207 http://dx.doi.org/10.1073/pnas.2213186120 |
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