Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion

The invasive potential of cancer cells strongly depends on cellular stiffness, a physical quantity that is not only regulated by the mechanical impact of the cytoskeleton but also influenced by the membrane rigidity. To analyze the specific role of membrane rigidity in cancer progression, we treated...

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Main Authors: Simone Braig, B U Sebastian Schmidt, Katharina Stoiber, Chris Händel, Till Möhn, Oliver Werz, Rolf Müller, Stefan Zahler, Andreas Koeberle, Josef A Käs, Angelika M Vollmar
Format: Article
Language:English
Published: IOP Publishing 2015-01-01
Series:New Journal of Physics
Subjects:
Online Access:https://doi.org/10.1088/1367-2630/17/8/083007
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author Simone Braig
B U Sebastian Schmidt
Katharina Stoiber
Chris Händel
Till Möhn
Oliver Werz
Rolf Müller
Stefan Zahler
Andreas Koeberle
Josef A Käs
Angelika M Vollmar
author_facet Simone Braig
B U Sebastian Schmidt
Katharina Stoiber
Chris Händel
Till Möhn
Oliver Werz
Rolf Müller
Stefan Zahler
Andreas Koeberle
Josef A Käs
Angelika M Vollmar
author_sort Simone Braig
collection DOAJ
description The invasive potential of cancer cells strongly depends on cellular stiffness, a physical quantity that is not only regulated by the mechanical impact of the cytoskeleton but also influenced by the membrane rigidity. To analyze the specific role of membrane rigidity in cancer progression, we treated cancer cells with the Acetyl-CoA carboxylase inhibitor Soraphen A and revealed an alteration of the phospholipidome via mass spectrometry. Migration, invasion, and cell death assays were employed to relate this alteration to functional consequences, and a decrease of migration and invasion without significant impact on cell death has been recorded. Fourier fluctuation analysis of giant plasma membrane vesicles showed that Soraphen A increases membrane rigidity of carcinoma cell membranes. Mechanical measurements of the creep deformation response of whole intact cells were performed using the optical stretcher. The increase in membrane rigidity was observed in one cell line without changing the creep deformation response indicating no restructuring of the cytoskeleton. These data indicate that the increase of membrane rigidity alone is sufficient to inhibit invasiveness of cancer cells, thus disclosing the eminent role of membrane rigidity in migratory processes.
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spelling doaj.art-dda7d94c296e4bb6a9b830a92ffad63d2023-08-08T14:21:04ZengIOP PublishingNew Journal of Physics1367-26302015-01-0117808300710.1088/1367-2630/17/8/083007Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasionSimone Braig0B U Sebastian Schmidt1Katharina Stoiber2Chris Händel3Till Möhn4Oliver Werz5Rolf Müller6Stefan Zahler7Andreas Koeberle8Josef A Käs9Angelika M Vollmar10Department of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Ludwig-Maximilians University , Butenandtstr. 5-13, D-81377 Munich, GermanyFaculty of Physics and Earth Sciences, Institute of Experimental Physics I, Leipzig University , Linnéstr. 5, D-04103 Leipzig, GermanyDepartment of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Ludwig-Maximilians University , Butenandtstr. 5-13, D-81377 Munich, GermanyFaculty of Physics and Earth Sciences, Institute of Experimental Physics I, Leipzig University , Linnéstr. 5, D-04103 Leipzig, GermanyFaculty of Physics and Earth Sciences, Institute of Experimental Physics I, Leipzig University , Linnéstr. 5, D-04103 Leipzig, GermanyInstitute of Pharmacy, University Jena , Philosophenweg 14, D-07743 Jena, GermanyHelmholtz Centre for Infection Research and Department of Pharmaceutical Biotechnology, Helmholtz Institute for Pharmaceutical Research Saarland, Saarland University , PO 151150, D-66042 Saarbrücken, GermanyDepartment of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Ludwig-Maximilians University , Butenandtstr. 5-13, D-81377 Munich, GermanyInstitute of Pharmacy, University Jena , Philosophenweg 14, D-07743 Jena, GermanyFaculty of Physics and Earth Sciences, Institute of Experimental Physics I, Leipzig University , Linnéstr. 5, D-04103 Leipzig, GermanyDepartment of Pharmacy, Center for Drug Research, Pharmaceutical Biology, Ludwig-Maximilians University , Butenandtstr. 5-13, D-81377 Munich, GermanyThe invasive potential of cancer cells strongly depends on cellular stiffness, a physical quantity that is not only regulated by the mechanical impact of the cytoskeleton but also influenced by the membrane rigidity. To analyze the specific role of membrane rigidity in cancer progression, we treated cancer cells with the Acetyl-CoA carboxylase inhibitor Soraphen A and revealed an alteration of the phospholipidome via mass spectrometry. Migration, invasion, and cell death assays were employed to relate this alteration to functional consequences, and a decrease of migration and invasion without significant impact on cell death has been recorded. Fourier fluctuation analysis of giant plasma membrane vesicles showed that Soraphen A increases membrane rigidity of carcinoma cell membranes. Mechanical measurements of the creep deformation response of whole intact cells were performed using the optical stretcher. The increase in membrane rigidity was observed in one cell line without changing the creep deformation response indicating no restructuring of the cytoskeleton. These data indicate that the increase of membrane rigidity alone is sufficient to inhibit invasiveness of cancer cells, thus disclosing the eminent role of membrane rigidity in migratory processes.https://doi.org/10.1088/1367-2630/17/8/083007membrane biophysicsbiomechanicsphysics of cancer87.16.D- or 87.16.dm
spellingShingle Simone Braig
B U Sebastian Schmidt
Katharina Stoiber
Chris Händel
Till Möhn
Oliver Werz
Rolf Müller
Stefan Zahler
Andreas Koeberle
Josef A Käs
Angelika M Vollmar
Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion
New Journal of Physics
membrane biophysics
biomechanics
physics of cancer
87.16.D- or 87.16.dm
title Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion
title_full Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion
title_fullStr Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion
title_full_unstemmed Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion
title_short Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion
title_sort pharmacological targeting of membrane rigidity implications on cancer cell migration and invasion
topic membrane biophysics
biomechanics
physics of cancer
87.16.D- or 87.16.dm
url https://doi.org/10.1088/1367-2630/17/8/083007
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