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iScience. 2020 Mar 27;23(3):100907. doi: 10.1016/j.isci.2020.100907. Epub 2020 Feb 13.

Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts.

Author information

1
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland.
2
Institute for Bioengineering of Catalonia, University of Barcelona, Barcelona 08028, Spain.
3
University of Bergen, 5020 Bergen, Norway.
4
Institute for Bioengineering of Catalonia, University of Barcelona, Barcelona 08028, Spain; University of Barcelona, Barcelona 08028, Spain.
5
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Institute of Biomedicine and Cancer Research Laboratory FICAN West, University of Turku, FI-20520 Turku, Finland. Electronic address: emilia.peuhu@utu.fi.
6
Turku Bioscience Centre, University of Turku and Åbo Akademi University, FI-20520 Turku, Finland; Department of Biochemistry, University of Turku, FI-20520 Turku, Finland. Electronic address: johanna.ivaska@utu.fi.

Abstract

The link between integrin activity regulation and cellular mechanosensing of tissue rigidity, especially on different extracellular matrix ligands, remains poorly understood. Here, we find that primary mouse mammary gland stromal fibroblasts (MSFs) are able to spread efficiently, generate high forces, and display nuclear YAP on soft collagen-coated substrates, resembling the soft mammary gland tissue. We describe that loss of the integrin inhibitor, SHARPIN, impedes MSF spreading specifically on soft type I collagen but not on fibronectin. Through quantitative experiments and computational modeling, we find that SHARPIN-deficient MSFs display faster force-induced unbinding of adhesions from collagen-coated beads. Faster unbinding, in turn, impairs force transmission in these cells, particularly, at the stiffness optimum observed for wild-type cells. Mechanistically, we link the impaired mechanotransduction of SHARPIN-deficient cells on collagen to reduced levels of collagen-binding integrin α11β1. Thus integrin activity regulation and α11β1 play a role in collagen-specific mechanosensing in MSFs.

KEYWORDS:

Biological Sciences; Cell Biology; Functional Aspects of Cell Biology

Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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