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Unravelling the force-induced dynamics of integrin-based adhesion complexes

Författare

Summary, in English

A cell’s ability to sense and respond to mechanical cues from its extracellular environment is essential for maintaining the health of itself and its organism. The mechanical cues a cell encounters include physical forces such as shear, tensile, and compressive forces, as well as cues arising from the mechanical properties of the extracellular matrix (ECM), such as stiffness or composition. Through mechanotransduction, a cell converts these mechanical cues into biochemical signals that control a wide range of functions, such as differentiation, morphogenesis, cell migration, and apoptosis.
integrin-based adhesion complexes (IACs) are one of the primary mechanisms of mechanotransduction. These large protein structures transmit mechanical signals between the ECM and the cell’s actomyosin cytoskeleton. In this thesis we investigate changes in IAC composition in response to externally applied forces and identify and study individual force-sensitive IAC proteins.
To investigate changes in IAC composition in response to varying durations of externally applied forces, we first combined a magnetic bead-based isolation assay with mass spectrometry. This approach revealed dynamic, force-duration-dependent changes in IAC composition. With prolonged force application, IACs transitioned from clathrin-rich structures to more focal adhesion-like structures, and ultimately to structures highly enriched in translational proteins.
Next, we focused our investigation on Sept-7 and Larp1, identified in our studies as highly force-sensitive proteins. We found that Sept-7 influences the stabilization and maturation of IACs and plays a crucial role in ECM sensing and remodeling. While Larp1 is well-documented as a regulator of translation, our studies identify it as a bona fide force-sensitive IAC protein.
Knowledge gained from this thesis advances our understanding of IACs, particularly their dynamic and adaptable responses to mechanical cues. Moreover, it underscores how much more remains to be discovered about these complex and fascinating structures.

Publiceringsår

2025

Språk

Engelska

Publikation/Tidskrift/Serie

Lund University, Faculty of Medicine Doctoral Dissertation Series

Issue

2025:11

Dokumenttyp

Doktorsavhandling

Förlag

Lund University, Faculty of Medicine

Ämne

  • Cell and Molecular Biology
  • Cancer and Oncology

Nyckelord

  • mechnobiology
  • Integrin-based adhesion complexes
  • focal adhesions
  • fibroblasts
  • Larp1
  • Sept-7
  • Septins
  • Mechanotransduction, Cellular

Aktiv

Published

ISBN/ISSN/Övrigt

  • ISSN: 1652-8220
  • ISBN: 978-91-8021-664-7

Försvarsdatum

7 februari 2025

Försvarstid

13:00

Försvarsplats

Belfragesalen, BMC D15, Klinikgatan 32 i Lund

Opponent

  • Ben Goult (Professor)