Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization
Local substrate stiffness is one of the major mechanical inputs for tissue organization during its development and remodeling. It is widely recognized that adherent cells use transmembrane proteins (integrins) at focal adhesions to translate ECM mechanical cues into intracellular bioprocess. Here we...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1198109/full |
| _version_ | 1797821442322071552 |
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| author | Deekshitha Jetta Tasnim Shireen Susan Z. Hua Susan Z. Hua |
| author_facet | Deekshitha Jetta Tasnim Shireen Susan Z. Hua Susan Z. Hua |
| author_sort | Deekshitha Jetta |
| collection | DOAJ |
| description | Local substrate stiffness is one of the major mechanical inputs for tissue organization during its development and remodeling. It is widely recognized that adherent cells use transmembrane proteins (integrins) at focal adhesions to translate ECM mechanical cues into intracellular bioprocess. Here we show that epithelial cells respond to substrate stiffening primarily via actin cytoskeleton organization, that requires activation of mechanosensitive Piezo1 channels. Piezo1 Knockdown cells eliminated the actin stress fibers that formed on stiff substrates, while it had minimal effect on cell morphology and spreading area. Inhibition of Piezo1 channels with GsMTx4 also significantly reduced stiffness-induced F-actin reorganization, suggesting Piezo1 mediated cation current plays a role. Activation of Piezo1 channels with specific agonist (Yoda1) resulted in thickening of F-actin fibers and enlargement of FAs on stiffer substrates, whereas it did not affect the formation of nascent FAs that facilitate spreading on the soft substrates. These results demonstrate that Piezo1 functions as a force sensor that couples with actin cytoskeleton to distinguish the substrate stiffness and facilitate epithelial adaptive remodeling. |
| first_indexed | 2024-03-13T09:52:45Z |
| format | Article |
| id | doaj.art-a156f9e716e244ab92a15e749adb9dfc |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-13T09:52:45Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-a156f9e716e244ab92a15e749adb9dfc2023-05-24T06:08:52ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-05-011110.3389/fcell.2023.11981091198109Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganizationDeekshitha Jetta0Tasnim Shireen1Susan Z. Hua2Susan Z. Hua3Department of Mechanical and Aerospace Engineering, University at Buffalo, Buffalo, NY, United StatesDepartment of Mechanical and Aerospace Engineering, University at Buffalo, Buffalo, NY, United StatesDepartment of Mechanical and Aerospace Engineering, University at Buffalo, Buffalo, NY, United StatesDepartment of Physiology and Biophysics, University at Buffalo, Buffalo, NY, United StatesLocal substrate stiffness is one of the major mechanical inputs for tissue organization during its development and remodeling. It is widely recognized that adherent cells use transmembrane proteins (integrins) at focal adhesions to translate ECM mechanical cues into intracellular bioprocess. Here we show that epithelial cells respond to substrate stiffening primarily via actin cytoskeleton organization, that requires activation of mechanosensitive Piezo1 channels. Piezo1 Knockdown cells eliminated the actin stress fibers that formed on stiff substrates, while it had minimal effect on cell morphology and spreading area. Inhibition of Piezo1 channels with GsMTx4 also significantly reduced stiffness-induced F-actin reorganization, suggesting Piezo1 mediated cation current plays a role. Activation of Piezo1 channels with specific agonist (Yoda1) resulted in thickening of F-actin fibers and enlargement of FAs on stiffer substrates, whereas it did not affect the formation of nascent FAs that facilitate spreading on the soft substrates. These results demonstrate that Piezo1 functions as a force sensor that couples with actin cytoskeleton to distinguish the substrate stiffness and facilitate epithelial adaptive remodeling.https://www.frontiersin.org/articles/10.3389/fcell.2023.1198109/fullPiezo1 channelsECM stiffnessmechanobiologyMDCK cellsfocal adhesionsepithelial remolding |
| spellingShingle | Deekshitha Jetta Tasnim Shireen Susan Z. Hua Susan Z. Hua Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization Frontiers in Cell and Developmental Biology Piezo1 channels ECM stiffness mechanobiology MDCK cells focal adhesions epithelial remolding |
| title | Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization |
| title_full | Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization |
| title_fullStr | Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization |
| title_full_unstemmed | Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization |
| title_short | Epithelial cells sense local stiffness via Piezo1 mediated cytoskeletal reorganization |
| title_sort | epithelial cells sense local stiffness via piezo1 mediated cytoskeletal reorganization |
| topic | Piezo1 channels ECM stiffness mechanobiology MDCK cells focal adhesions epithelial remolding |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1198109/full |
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