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Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis.

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 mechanosensitive 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 stiffness 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 contributes to ECM mechanics, directly supporting the mechanical homeostasis hypothesis and identifying a mechanosensitive interaction within talin that contributes to this mechanism.

SUBMITTER: Chanduri M

PROVIDER: S-EPMC11338229 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis.

Chanduri Manasa M Kumar Abhishek A Weiss Dar D Emuna Nir N Barsukov Igor I Shi Miusi M Tanaka Keiichiro K Wang Xinzhe X Datye Amit A Kanyo Jean J Collin Florine F Lam TuKiet T Schwarz Udo D UD Bai Suxia S Nottoli Timothy T Goult Benjamin T BT Humphrey Jay D JD Schwartz Martin A MA

Science advances 20240821 34

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 mechanosensitive 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 spreadin ...[more]

PMID: 39167642

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Dataset Information

Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis.

Publications

Cellular stiffness sensing through talin 1 in tissue mechanical homeostasis.

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