MARC details
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04828ntm a22003377a 4500 |
| 003 - CONTROL NUMBER IDENTIFIER |
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AT-ISTA |
| 005 - DATE AND TIME OF LATEST TRANSACTION |
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20200723083751.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION |
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200723s2019 au ||||| m||| 00| 0 eng d |
| 040 ## - CATALOGING SOURCE |
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| Transcribing agency |
IST |
| 100 ## - MAIN ENTRY--PERSONAL NAME |
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| Personal name |
Kopf, Aglaja |
| 9 (RLIN) |
215076 |
| 245 ## - TITLE STATEMENT |
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| Title |
The implication of cytoskeletal dynamics during leukocyte migration |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. (IMPRINT) |
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| Name of publisher, distributor, etc. |
IST Austria |
| Date of publication, distribution, etc. |
2019 |
| 500 ## - GENERAL NOTE |
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| General note |
Thesis |
| 505 ## - FORMATTED CONTENTS NOTE |
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| Formatted contents note |
Abstract |
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Acknowledgments |
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About the Author |
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| Formatted contents note |
List of Publications Appearing in Thesis |
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| Formatted contents note |
List of Figures |
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List of Tables |
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List of Symbols and Abbreviations |
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| Formatted contents note |
1. Cell migration - an introduction |
| 505 ## - FORMATTED CONTENTS NOTE |
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| Formatted contents note |
2. Aim of the thesis and initial status |
| 505 ## - FORMATTED CONTENTS NOTE |
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3. The role of the microtubule cytoskeleton during cell migration |
| 505 ## - FORMATTED CONTENTS NOTE |
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4. Principles of force generation and transduction |
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5. Material and Methods |
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6. Editorial articles |
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References |
| 520 ## - SUMMARY, ETC. |
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| Summary, etc. |
While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. Cells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. Nevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. Therefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. The results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. Thus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. Thereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance. |
| 856 ## - ELECTRONIC LOCATION AND ACCESS |
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| Uniform Resource Identifier |
<a href="https://doi.org/10.15479/AT:ISTA:6891">https://doi.org/10.15479/AT:ISTA:6891</a> |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) |
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| Source of classification or shelving scheme |
Dewey Decimal Classification |