Unravelling the force-induced dynamics of integrin-based adhesion complexes
(2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series- Abstract
- 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... (More) - 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.
(Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3c0336d5-a35e-4ba1-8df7-e10f7ec9ad3a
- author
- Sturgess, Wesley LU
- supervisor
- opponent
-
- Professor Goult, Ben, University of Liverpool
- organization
- publishing date
- 2025
- type
- Thesis
- publication status
- published
- subject
- keywords
- mechnobiology, Integrin-based adhesion complexes, focal adhesions, fibroblasts, Larp1, Sept-7, Septins, Mechanotransduction, Cellular
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- issue
- 2025:11
- pages
- 71 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund
- defense date
- 2025-02-07 13:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-664-7
- language
- English
- LU publication?
- yes
- id
- 3c0336d5-a35e-4ba1-8df7-e10f7ec9ad3a
- date added to LUP
- 2025-01-15 10:21:57
- date last changed
- 2025-04-04 14:09:19
@phdthesis{3c0336d5-a35e-4ba1-8df7-e10f7ec9ad3a,
abstract = {{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. <br/>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. <br/>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. <br/>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. <br/>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.<br/>}},
author = {{Sturgess, Wesley}},
isbn = {{978-91-8021-664-7}},
issn = {{1652-8220}},
keywords = {{mechnobiology; Integrin-based adhesion complexes; focal adhesions; fibroblasts; Larp1; Sept-7; Septins; Mechanotransduction, Cellular}},
language = {{eng}},
number = {{2025:11}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Unravelling the force-induced dynamics of integrin-based adhesion complexes}},
url = {{https://lup.lub.lu.se/search/files/206043667/Wesley_Sturgess_-_WEBB.pdf}},
year = {{2025}},
}