Integrin force loading rate in mechanobiology: From model to molecular measurement
Integrins are critical transmembrane receptors that connect the extracellular matrix (ECM) to the intracellular cytoskeleton, playing a central role in mechanotransduction – the process by which cells convert mechanical stimuli into biochemical signals. The dynamic assembly and disassembly of integr...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2025-01-01
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| Series: | QRB Discovery |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S2633289224000280/type/journal_article |
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| author | Hongyuan Zhang Micah Yang Seong Ho Kim Isaac T.S. Li |
| author_facet | Hongyuan Zhang Micah Yang Seong Ho Kim Isaac T.S. Li |
| author_sort | Hongyuan Zhang |
| collection | DOAJ |
| description | Integrins are critical transmembrane receptors that connect the extracellular matrix (ECM) to the intracellular cytoskeleton, playing a central role in mechanotransduction – the process by which cells convert mechanical stimuli into biochemical signals. The dynamic assembly and disassembly of integrin-mediated adhesions enable cells to adapt continuously to changing mechanical cues, regulating essential processes such as adhesion, migration, and proliferation. In this review, we explore the molecular clutch model as a framework for understanding the dynamics of integrin – ECM interactions, emphasizing the critical importance of force loading rate. We discuss how force loading rate bridges internal actomyosin-generated forces and ECM mechanical properties like stiffness and ligand density, determining whether sufficient force is transmitted to mechanosensitive proteins such as talin. This force transmission leads to talin unfolding and activation of downstream signalling pathways, ultimately influencing cellular responses. We also examine recent advances in single-molecule DNA tension sensors that have enabled direct measurements of integrin loading rates, refining the range to approximately 0.5–4 pN/s. These findings deepen our understanding of force-mediated mechanotransduction and underscore the need for improved sensor designs to overcome current limitations. |
| format | Article |
| id | doaj-art-9eaeb17a452e43c5bc354007c233dcdc |
| institution | DOAJ |
| issn | 2633-2892 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | QRB Discovery |
| spelling | doaj-art-9eaeb17a452e43c5bc354007c233dcdc2025-08-20T02:57:37ZengCambridge University PressQRB Discovery2633-28922025-01-01610.1017/qrd.2024.28Integrin force loading rate in mechanobiology: From model to molecular measurementHongyuan Zhang0https://orcid.org/0009-0006-1091-3251Micah Yang1https://orcid.org/0009-0006-9822-2892Seong Ho Kim2Isaac T.S. Li3https://orcid.org/0000-0002-8450-5326Department of Chemistry, The University of British Columbia, Kelowna, BC, CanadaDepartment of Chemistry, The University of British Columbia, Kelowna, BC, CanadaDepartment of Chemistry, The University of British Columbia, Kelowna, BC, CanadaDepartment of Chemistry, The University of British Columbia, Kelowna, BC, CanadaIntegrins are critical transmembrane receptors that connect the extracellular matrix (ECM) to the intracellular cytoskeleton, playing a central role in mechanotransduction – the process by which cells convert mechanical stimuli into biochemical signals. The dynamic assembly and disassembly of integrin-mediated adhesions enable cells to adapt continuously to changing mechanical cues, regulating essential processes such as adhesion, migration, and proliferation. In this review, we explore the molecular clutch model as a framework for understanding the dynamics of integrin – ECM interactions, emphasizing the critical importance of force loading rate. We discuss how force loading rate bridges internal actomyosin-generated forces and ECM mechanical properties like stiffness and ligand density, determining whether sufficient force is transmitted to mechanosensitive proteins such as talin. This force transmission leads to talin unfolding and activation of downstream signalling pathways, ultimately influencing cellular responses. We also examine recent advances in single-molecule DNA tension sensors that have enabled direct measurements of integrin loading rates, refining the range to approximately 0.5–4 pN/s. These findings deepen our understanding of force-mediated mechanotransduction and underscore the need for improved sensor designs to overcome current limitations.https://www.cambridge.org/core/product/identifier/S2633289224000280/type/journal_articleDNA-based tension sensorintegrinloading ratemechanotransductionmolecular clutchsingle-molecule force imaging |
| spellingShingle | Hongyuan Zhang Micah Yang Seong Ho Kim Isaac T.S. Li Integrin force loading rate in mechanobiology: From model to molecular measurement QRB Discovery DNA-based tension sensor integrin loading rate mechanotransduction molecular clutch single-molecule force imaging |
| title | Integrin force loading rate in mechanobiology: From model to molecular measurement |
| title_full | Integrin force loading rate in mechanobiology: From model to molecular measurement |
| title_fullStr | Integrin force loading rate in mechanobiology: From model to molecular measurement |
| title_full_unstemmed | Integrin force loading rate in mechanobiology: From model to molecular measurement |
| title_short | Integrin force loading rate in mechanobiology: From model to molecular measurement |
| title_sort | integrin force loading rate in mechanobiology from model to molecular measurement |
| topic | DNA-based tension sensor integrin loading rate mechanotransduction molecular clutch single-molecule force imaging |
| url | https://www.cambridge.org/core/product/identifier/S2633289224000280/type/journal_article |
| work_keys_str_mv | AT hongyuanzhang integrinforceloadingrateinmechanobiologyfrommodeltomolecularmeasurement AT micahyang integrinforceloadingrateinmechanobiologyfrommodeltomolecularmeasurement AT seonghokim integrinforceloadingrateinmechanobiologyfrommodeltomolecularmeasurement AT isaactsli integrinforceloadingrateinmechanobiologyfrommodeltomolecularmeasurement |