Amiri, Anahid (2024)
Probing Cytoskeletal Scaffolding and
Mechanical Integrity of Cells in Disease
with Atomic Force Microscopy.
Technische Universität Darmstadt
doi: 10.26083/tuprints-00027883
Ph.D. Thesis, Primary publication, Publisher's Version
Text
Probing Cytoskeletal Scaffolding and Mechanical Integrity of Cells in Disease with Atomic Force Microscopy.pdf Copyright Information: In Copyright. Download (116MB) |
Item Type: | Ph.D. Thesis | ||||
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Type of entry: | Primary publication | ||||
Title: | Probing Cytoskeletal Scaffolding and Mechanical Integrity of Cells in Disease with Atomic Force Microscopy | ||||
Language: | English | ||||
Referees: | Stark, Prof. Dr. Robert ; Cardoso, Prof. Dr. M. Cristina | ||||
Date: | 4 September 2024 | ||||
Place of Publication: | Darmstadt | ||||
Collation: | 172 Seiten in verschiedenen Zählungen | ||||
Date of oral examination: | 9 July 2024 | ||||
DOI: | 10.26083/tuprints-00027883 | ||||
Abstract: | The morphological, structural, and mechanical alterations of cancer cells are pivotal during cancer development, facilitating effective metastasis. In this regard, understanding cytoskeletal changes in cancer is essential for developing targeted therapeutic strategies aimed at disrupting cancer cells’ progression in invasion, and metastasis through cytoskeletal manipulations. In this dissertation high-resolution quantitative nanomechanical characterization, 3D stiffness tomography, and 3D confocal microscopy were employed to examine the cellular cytoskeleton scaffolding and its integrity within cancer cells. This in-depth exploration of mechanical and physical variances associated with cellular transformations in cancer provided an extensive analysis of the mechanical and dynamic changes of cytoskeletal elements in epithelial-type progressive cancers through several contact mechanics models and filaments’ persistence length measure. Our investigation primarily centered on breast cancer cells, highlighting the roles of microtubules and the cytolinker protein plectin in reducing cellular stiffness compared to normal cells. These findings were then extrapolated to other lethal cancers, including those affecting the liver, lung, and skin, to understand broader implications. We found significant variability in cytoskeletal filament expression and configuration, primarily due to the positioning of basal microtubules caused by cytoskeletal cross-linking disruptions. Paclitaxel, a cytoskeletal stabilizing drug, was shown to restore the microtubule network and plectin cytoskeletal structure in invasive carcinoma cells. It facilitated the reassembly of microtubules beneath the cell membrane and repositioned plectin, enhancing cellular mechanical integrity. Additionally, paclitaxel increased the correlation between tubulin and actin, suggesting enhanced cytoskeletal organization. This reorganization involving the three primary cytoskeletal components, may reduce the malignant cell's ability to extend across the anatomical micropores, that requires further study. |
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Status: | Publisher's Version | ||||
URN: | urn:nbn:de:tuda-tuprints-278835 | ||||
Classification DDC: | 500 Science and mathematics > 500 Science 500 Science and mathematics > 530 Physics 500 Science and mathematics > 570 Life sciences, biology |
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Divisions: | 11 Department of Materials and Earth Sciences > Material Science > Physics of Surfaces | ||||
Date Deposited: | 04 Sep 2024 06:48 | ||||
Last Modified: | 05 Sep 2024 06:15 | ||||
URI: | https://tuprints.ulb.tu-darmstadt.de/id/eprint/27883 | ||||
PPN: | 521098750 | ||||
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