Chanduri, Manasa, Kumar, Abhishek, Weiss, Dar, Emuna, Nir, Barsukov, Igor L, Shi, Miushi, Tanaka, Keiichiro, Wang, Xinzhe, Datye, Amit, Kanyo, Jean, and others. (2024) Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis. Science Advances, 10 (34). Article Number eadi6286. ISSN 2375-2548. (doi:10.1126/sciadv.adi6286) (KAR id:107015)
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| Official URL: https://doi.org/10.1126/sciadv.adi6286 |
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Abstract
Tissue mechanical properties are determined mainly by the extracellular matrix (ECM) and actively maintained by resident cells. Despite its broad importance to biology and medicine, tissue mechanical homeostasis remains poorly understood. To explore cell-mediated control of tissue stiffness, we developed mutations in the mechano- sensitive protein talin 1 to alter cellular sensing of ECM. Mutation of a mechanosensitive site between talin 1 rod- domain helix bundles R1 and R2 increased cell spreading and tension exertion on compliant substrates. These mutations promote binding of the ARP2/3 complex subunit ARPC5L, which mediates the change in substrate stiff- ness sensing. Ascending aortas from mice bearing these mutations showed less fibrillar collagen, reduced axial stiffness, and lower rupture pressure. Together, these results demonstrate that cellular stiffness sensing contrib- utes to ECM mechanics, directly supporting the mechanical homeostasis hypothesis and identifying a mechano- sensitive interaction within talin that contributes to this mechanism.
| Item Type: | Article |
|---|---|
| DOI/Identification number: | 10.1126/sciadv.adi6286 |
| Uncontrolled keywords: | Extracellular Matrix - metabolism, Mice, Protein Binding, Biomechanical Phenomena, Mechanotransduction, Cellular, Talin - metabolism - genetics, Aorta - metabolism, Mutation, Homeostasis, Animals, Humans, Actin-Related Protein 2-3 Complex - metabolism - genetics |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | Divisions > Division of Natural Sciences > Biosciences |
| Funders: | University of Kent (https://ror.org/00xkeyj56) |
| Depositing User: | Ben Goult |
| Date Deposited: | 27 Aug 2024 08:40 UTC |
| Last Modified: | 06 Sep 2024 13:31 UTC |
| Resource URI: | https://kar.kent.ac.uk/id/eprint/107015 (The current URI for this page, for reference purposes) |
University of Kent Author Information
Goult, Benjamin T.
| Creator's ORCID: |
 https://orcid.org/0000-0002-3438-2807
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