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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...

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Autores principales: Skamrahl, Mark, Schünemann, Justus, Mukenhirn, Markus, Pang, Hongtao, Gottwald, Jannis, Jipp, Marcel, Ferle, Maximilian, Rübeling, Angela, Oswald, Tabea A., Honigmann, Alf, Janshoff , Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2023
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.
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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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