Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence

Abstract Cellular senescence is a phenotype characterized by cessation of cell division, which can be caused by exhaustive replication or environmental stress. It is involved in age-related pathophysiological conditions and affects both the cellular cytoskeleton and the prime cellular mechanosensors...

Full description

Bibliographic Details
Main Authors: Carolin Grandy, Fabian Port, Meytal Radzinski, Karmveer Singh, Dorothee Erz, Jonas Pfeil, Dana Reichmann, Kay-Eberhard Gottschalk
Format: Article
Language:English
Published: Nature Portfolio 2023-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-36347-2
_version_ 1797801452873187328
author Carolin Grandy
Fabian Port
Meytal Radzinski
Karmveer Singh
Dorothee Erz
Jonas Pfeil
Dana Reichmann
Kay-Eberhard Gottschalk
author_facet Carolin Grandy
Fabian Port
Meytal Radzinski
Karmveer Singh
Dorothee Erz
Jonas Pfeil
Dana Reichmann
Kay-Eberhard Gottschalk
author_sort Carolin Grandy
collection DOAJ
description Abstract Cellular senescence is a phenotype characterized by cessation of cell division, which can be caused by exhaustive replication or environmental stress. It is involved in age-related pathophysiological conditions and affects both the cellular cytoskeleton and the prime cellular mechanosensors, focal adhesion complexes. While the size of focal adhesions increases during senescence, it is unknown if and how this is accompanied by a remodeling of the internal focal adhesion structure. Our study uses metal-induced energy transfer to study the axial dimension of focal adhesion proteins from oxidative-stress-induced senescent cells with nanometer precision, and compares these to unstressed cells. We influenced cytoskeletal tension and the functioning of mechanosensitive ion channels using drugs and studied the combined effect of senescence and drug intervention on the focal adhesion structure. We found that H2O2-induced restructuring of the focal adhesion complex indicates a loss of tension and altered talin complexation. Mass spectroscopy-based proteomics confirmed the differential regulation of several cytoskeletal proteins induced by H2O2 treatment.
first_indexed 2024-03-13T04:50:42Z
format Article
id doaj.art-9c01751e1b5b4967a557497b913636f1
institution Directory Open Access Journal
issn 2045-2322
language English
last_indexed 2024-03-13T04:50:42Z
publishDate 2023-06-01
publisher Nature Portfolio
record_format Article
series Scientific Reports
spelling doaj.art-9c01751e1b5b4967a557497b913636f12023-06-18T11:13:32ZengNature PortfolioScientific Reports2045-23222023-06-0113111710.1038/s41598-023-36347-2Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescenceCarolin Grandy0Fabian Port1Meytal Radzinski2Karmveer Singh3Dorothee Erz4Jonas Pfeil5Dana Reichmann6Kay-Eberhard Gottschalk7Institute of Experimental Physics, Ulm UniversityInstitute of Experimental Physics, Ulm UniversityAlexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus-Givat RamDepartment of Dermatology and Allergic Diseases, Ulm UniversityInstitute of Experimental Physics, Ulm UniversityInstitute of Experimental Physics, Ulm UniversityAlexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Edmond J. Safra Campus-Givat RamInstitute of Experimental Physics, Ulm UniversityAbstract Cellular senescence is a phenotype characterized by cessation of cell division, which can be caused by exhaustive replication or environmental stress. It is involved in age-related pathophysiological conditions and affects both the cellular cytoskeleton and the prime cellular mechanosensors, focal adhesion complexes. While the size of focal adhesions increases during senescence, it is unknown if and how this is accompanied by a remodeling of the internal focal adhesion structure. Our study uses metal-induced energy transfer to study the axial dimension of focal adhesion proteins from oxidative-stress-induced senescent cells with nanometer precision, and compares these to unstressed cells. We influenced cytoskeletal tension and the functioning of mechanosensitive ion channels using drugs and studied the combined effect of senescence and drug intervention on the focal adhesion structure. We found that H2O2-induced restructuring of the focal adhesion complex indicates a loss of tension and altered talin complexation. Mass spectroscopy-based proteomics confirmed the differential regulation of several cytoskeletal proteins induced by H2O2 treatment.https://doi.org/10.1038/s41598-023-36347-2
spellingShingle Carolin Grandy
Fabian Port
Meytal Radzinski
Karmveer Singh
Dorothee Erz
Jonas Pfeil
Dana Reichmann
Kay-Eberhard Gottschalk
Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence
Scientific Reports
title Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence
title_full Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence
title_fullStr Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence
title_full_unstemmed Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence
title_short Remodeling of the focal adhesion complex by hydrogen-peroxide-induced senescence
title_sort remodeling of the focal adhesion complex by hydrogen peroxide induced senescence
url https://doi.org/10.1038/s41598-023-36347-2
work_keys_str_mv AT carolingrandy remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT fabianport remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT meytalradzinski remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT karmveersingh remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT dorotheeerz remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT jonaspfeil remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT danareichmann remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence
AT kayeberhardgottschalk remodelingofthefocaladhesioncomplexbyhydrogenperoxideinducedsenescence