Unravelling the force-induced dynamics of integrin-based adhesion complexes
Författare
Summary, in English
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
Fulltext
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
Handledare
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)