Chanduri, Manasa VL 
ORCID: 0000-0002-9353-1438, Kumar, Abhishek ORCID: 0000-0003-3235-1916, Weiss, Dar ORCID: 0000-0001-6097-6038, Emuna, Nir, Barsukov, Igor ORCID: 0000-0003-4406-9803, Shi, Muisi, Tanaka, Keiichiro ORCID: 0000-0001-6328-1485, Wang, Xinzhe, Datye, Amit ORCID: 0000-0002-1776-0642, Kanyo, Jean ORCID: 0000-0003-4814-7573 et al (show 8 more authors)
(2024)
Mechanosensing through talin 1 contributes to tissue mechanical homeostasis.
[Preprint]
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Abstract
It is widely believed that tissue mechanical properties, determined mainly by the extracellular matrix (ECM), are actively maintained. However, despite its broad importance to biology and medicine, tissue mechanical homeostasis is poorly understood. To explore this hypothesis, we developed mutations in the mechanosensitive protein talin1 that alter cellular sensing of ECM stiffness. Mutation of a novel mechanosensitive site between talin1 rod domain helix bundles 1 and 2 (R1 and R2) shifted cellular stiffness sensing curves, enabling cells to spread and exert tension on compliant substrates. Opening of the R1-R2 interface promotes binding of the ARP2/3 complex subunit ARPC5L, which mediates the altered stiffness sensing. Ascending aortas from mice bearing these mutations show increased compliance, less fibrillar collagen, and rupture at lower pressure. Together, these results demonstrate that cellular stiffness sensing regulates ECM mechanical properties. These data thus directly support the mechanical homeostasis hypothesis and identify a novel mechanosensitive interaction within talin that contributes to this mechanism.
| Item Type: | Preprint |
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| Uncontrolled Keywords: | Cardiovascular, Bioengineering, 1 Underpinning research, 2 Aetiology, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Generic health relevance |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 04 Mar 2024 09:25 |
| Last Modified: | 15 Mar 2024 20:50 |
| DOI: | 10.1101/2023.09.03.556084 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179046 |
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