Polarity signaling balances epithelial contractility and mechanical resistance
Abstract Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabl...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-33485-5 |
| _version_ | 1797827565150273536 |
|---|---|
| author | Matthias Rübsam Robin Püllen Frederik Tellkamp Alessandra Bianco Marc Peskoller Wilhelm Bloch Kathleen J. Green Rudolf Merkel Bernd Hoffmann Sara A. Wickström Carien M. Niessen |
| author_facet | Matthias Rübsam Robin Püllen Frederik Tellkamp Alessandra Bianco Marc Peskoller Wilhelm Bloch Kathleen J. Green Rudolf Merkel Bernd Hoffmann Sara A. Wickström Carien M. Niessen |
| author_sort | Matthias Rübsam |
| collection | DOAJ |
| description | Abstract Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabled by keratin filament-linked desmosomes. How these two systems crosstalk to coordinate cellular movement and mechanical resilience is not known. Here we show that in stratifying epithelia the polarity protein aPKCλ controls the reorganization from stress fibers to cortical actomyosin during differentiation and upward movement of cells. Without aPKC, stress fibers are retained resulting in increased contractile prestress. This aberrant stress is counterbalanced by reorganization and bundling of keratins, thereby increasing mechanical resilience. Inhibiting contractility in aPKCλ−/− cells restores normal cortical keratin networks but also normalizes resilience. Consistently, increasing contractile stress is sufficient to induce keratin bundling and enhance resilience, mimicking aPKC loss. In conclusion, our data indicate that keratins sense the contractile stress state of stratified epithelia and balance increased contractility by mounting a protective response to maintain tissue integrity. |
| first_indexed | 2024-04-09T12:50:21Z |
| format | Article |
| id | doaj.art-49b8af49c71147bfa299ecb65e9ed353 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-09T12:50:21Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-49b8af49c71147bfa299ecb65e9ed3532023-05-14T11:15:59ZengNature PortfolioScientific Reports2045-23222023-05-0113111410.1038/s41598-023-33485-5Polarity signaling balances epithelial contractility and mechanical resistanceMatthias Rübsam0Robin Püllen1Frederik Tellkamp2Alessandra Bianco3Marc Peskoller4Wilhelm Bloch5Kathleen J. Green6Rudolf Merkel7Bernd Hoffmann8Sara A. Wickström9Carien M. Niessen10Department Cell Biology of the Skin, University Hospital Cologne, University of CologneForschungszentrum Jülich, Institute of Biological Information Processing, IBI-2: MechanobiologyDepartment Cell Biology of the Skin, University Hospital Cologne, University of CologneDepartment Cell Biology of the Skin, University Hospital Cologne, University of CologneDepartment Cell Biology of the Skin, University Hospital Cologne, University of CologneDepartment of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sport Medicine, German Sport University of CologneDepartments of Pathology and Dermatology, Feinberg School of Medicine, Northwestern UniversityForschungszentrum Jülich, Institute of Biological Information Processing, IBI-2: MechanobiologyForschungszentrum Jülich, Institute of Biological Information Processing, IBI-2: MechanobiologyCologne Excellence Cluster for Stress Responses in Ageing-Associated Diseases (CECAD), University of CologneDepartment Cell Biology of the Skin, University Hospital Cologne, University of CologneAbstract Epithelia maintain a functional barrier during tissue turnover while facing varying mechanical stress. This maintenance requires both dynamic cell rearrangements driven by actomyosin-linked intercellular adherens junctions and ability to adapt to and resist extrinsic mechanical forces enabled by keratin filament-linked desmosomes. How these two systems crosstalk to coordinate cellular movement and mechanical resilience is not known. Here we show that in stratifying epithelia the polarity protein aPKCλ controls the reorganization from stress fibers to cortical actomyosin during differentiation and upward movement of cells. Without aPKC, stress fibers are retained resulting in increased contractile prestress. This aberrant stress is counterbalanced by reorganization and bundling of keratins, thereby increasing mechanical resilience. Inhibiting contractility in aPKCλ−/− cells restores normal cortical keratin networks but also normalizes resilience. Consistently, increasing contractile stress is sufficient to induce keratin bundling and enhance resilience, mimicking aPKC loss. In conclusion, our data indicate that keratins sense the contractile stress state of stratified epithelia and balance increased contractility by mounting a protective response to maintain tissue integrity.https://doi.org/10.1038/s41598-023-33485-5 |
| spellingShingle | Matthias Rübsam Robin Püllen Frederik Tellkamp Alessandra Bianco Marc Peskoller Wilhelm Bloch Kathleen J. Green Rudolf Merkel Bernd Hoffmann Sara A. Wickström Carien M. Niessen Polarity signaling balances epithelial contractility and mechanical resistance Scientific Reports |
| title | Polarity signaling balances epithelial contractility and mechanical resistance |
| title_full | Polarity signaling balances epithelial contractility and mechanical resistance |
| title_fullStr | Polarity signaling balances epithelial contractility and mechanical resistance |
| title_full_unstemmed | Polarity signaling balances epithelial contractility and mechanical resistance |
| title_short | Polarity signaling balances epithelial contractility and mechanical resistance |
| title_sort | polarity signaling balances epithelial contractility and mechanical resistance |
| url | https://doi.org/10.1038/s41598-023-33485-5 |
| work_keys_str_mv | AT matthiasrubsam polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT robinpullen polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT frederiktellkamp polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT alessandrabianco polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT marcpeskoller polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT wilhelmbloch polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT kathleenjgreen polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT rudolfmerkel polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT berndhoffmann polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT saraawickstrom polaritysignalingbalancesepithelialcontractilityandmechanicalresistance AT carienmniessen polaritysignalingbalancesepithelialcontractilityandmechanicalresistance |