Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration
Abstract Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin‐mediated binding to ligand...
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| Format: | Article |
| Language: | English |
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Wiley
2024-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202306497 |
| _version_ | 1797215302215270400 |
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| author | Seong‐Beom Han Geonhui Lee Daesan Kim Jeong‐Ki Kim In‐San Kim Hae‐Won Kim Dong‐Hwee Kim |
| author_facet | Seong‐Beom Han Geonhui Lee Daesan Kim Jeong‐Ki Kim In‐San Kim Hae‐Won Kim Dong‐Hwee Kim |
| author_sort | Seong‐Beom Han |
| collection | DOAJ |
| description | Abstract Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin‐mediated binding to ligand molecules. Although numerous biochemical pathways orchestrating cell adhesion and motility are identified, how subcellular forces between the cell and extracellular matrix regulate intracellular signaling for cell migration remains unclear. Here, it is showed that a molecular binding force across integrin subunits determines directional migration by regulating tension‐dependent focal contact formation and focal adhesion kinase phosphorylation. Molecular binding strength between integrin αvβ3 and fibronectin is precisely manipulated by developing molecular tension probes that control the mechanical tolerance applied to cell‐substrate interfaces. This data reveals that integrin‐mediated molecular binding force reduction suppresses cell spreading and focal adhesion formation, attenuating the focal adhesion kinase (FAK) phosphorylation that regulates the persistence of cell migration. These results further demonstrate that manipulating subcellular binding forces at the molecular level can recapitulate differential cell migration in response to changes of substrate rigidity that determines the physical condition of extracellular microenvironment. Novel insights is provided into the subcellular mechanics behind global mechanical adaptation of the cell to surrounding tissue environments featuring distinct biophysical signatures. |
| first_indexed | 2024-04-24T11:27:54Z |
| format | Article |
| id | doaj.art-97c8d97bf6444d42851bcd75b7f2f6c9 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-24T11:27:54Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-97c8d97bf6444d42851bcd75b7f2f6c92024-04-10T13:10:11ZengWileyAdvanced Science2198-38442024-04-011114n/an/a10.1002/advs.202306497Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell MigrationSeong‐Beom Han0Geonhui Lee1Daesan Kim2Jeong‐Ki Kim3In‐San Kim4Hae‐Won Kim5Dong‐Hwee Kim6KU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of KoreaKU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of KoreaKU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of KoreaKU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of KoreaKU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of KoreaInstitute of Tissue Regeneration Engineering (ITREN) Dankook University Cheonan 31116 Republic of KoreaKU‐KIST Graduate School of Converging Science and Technology Korea University Seoul 02841 Republic of KoreaAbstract Cell migration interacting with continuously changing microenvironment, is one of the most essential cellular functions, participating in embryonic development, wound repair, immune response, and cancer metastasis. The migration process is finely tuned by integrin‐mediated binding to ligand molecules. Although numerous biochemical pathways orchestrating cell adhesion and motility are identified, how subcellular forces between the cell and extracellular matrix regulate intracellular signaling for cell migration remains unclear. Here, it is showed that a molecular binding force across integrin subunits determines directional migration by regulating tension‐dependent focal contact formation and focal adhesion kinase phosphorylation. Molecular binding strength between integrin αvβ3 and fibronectin is precisely manipulated by developing molecular tension probes that control the mechanical tolerance applied to cell‐substrate interfaces. This data reveals that integrin‐mediated molecular binding force reduction suppresses cell spreading and focal adhesion formation, attenuating the focal adhesion kinase (FAK) phosphorylation that regulates the persistence of cell migration. These results further demonstrate that manipulating subcellular binding forces at the molecular level can recapitulate differential cell migration in response to changes of substrate rigidity that determines the physical condition of extracellular microenvironment. Novel insights is provided into the subcellular mechanics behind global mechanical adaptation of the cell to surrounding tissue environments featuring distinct biophysical signatures.https://doi.org/10.1002/advs.202306497cell adhesionFAK phosphorylationintegrin αvβ3molecular tension probespersistent migration |
| spellingShingle | Seong‐Beom Han Geonhui Lee Daesan Kim Jeong‐Ki Kim In‐San Kim Hae‐Won Kim Dong‐Hwee Kim Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration Advanced Science cell adhesion FAK phosphorylation integrin αvβ3 molecular tension probes persistent migration |
| title | Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration |
| title_full | Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration |
| title_fullStr | Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration |
| title_full_unstemmed | Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration |
| title_short | Selective Suppression of Integrin‐Ligand Binding by Single Molecular Tension Probes Mediates Directional Cell Migration |
| title_sort | selective suppression of integrin ligand binding by single molecular tension probes mediates directional cell migration |
| topic | cell adhesion FAK phosphorylation integrin αvβ3 molecular tension probes persistent migration |
| url | https://doi.org/10.1002/advs.202306497 |
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