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

Martina Lerche, Alberto Elosegui-Artola, Jenny Z. Kechagia, Camilo Guzmán, Maria Georgiadou, Ion Andreu, Donald Gullberg, Pere Roca-Cusachs, Emilia Peuhu, Johanna Ivaska

Research output: Contribution to journalArticleScientificpeer-review

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.
Original languageEnglish
Article number100907
JournaliScience
Volume23
Issue number3
DOIs
Publication statusPublished - 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • Biological Sciences
  • Cell Biology
  • Functional Aspects of Cell Biology

Fingerprint Dive into the research topics of 'Integrin Binding Dynamics Modulate Ligand-Specific Mechanosensing in Mammary Gland Fibroblasts'. Together they form a unique fingerprint.

Cite this