---
_id: '6891'
abstract:
- lang: eng
  text: "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. \r\nCells 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.
    \r\nNevertheless, 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. \r\nTherefore, 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. \r\nThe 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.
    \r\nThus, 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. \r\nThereby the here presented results help to further
    define fundamental principles underlying leukocyte migration and open up potential
    therapeutic avenues of clinical relevance.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Aglaja
  full_name: Kopf, Aglaja
  id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
  last_name: Kopf
  orcid: 0000-0002-2187-6656
citation:
  ama: Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019.
    doi:<a href="https://doi.org/10.15479/AT:ISTA:6891">10.15479/AT:ISTA:6891</a>
  apa: Kopf, A. (2019). <i>The implication of cytoskeletal dynamics on leukocyte migration</i>.
    Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT:ISTA:6891">https://doi.org/10.15479/AT:ISTA:6891</a>
  chicago: Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.”
    Institute of Science and Technology Austria, 2019. <a href="https://doi.org/10.15479/AT:ISTA:6891">https://doi.org/10.15479/AT:ISTA:6891</a>.
  ieee: A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,”
    Institute of Science and Technology Austria, 2019.
  ista: Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration.
    Institute of Science and Technology Austria.
  mla: Kopf, Aglaja. <i>The Implication of Cytoskeletal Dynamics on Leukocyte Migration</i>.
    Institute of Science and Technology Austria, 2019, doi:<a href="https://doi.org/10.15479/AT:ISTA:6891">10.15479/AT:ISTA:6891</a>.
  short: A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration,
    Institute of Science and Technology Austria, 2019.
date_created: 2019-09-19T08:19:44Z
date_published: 2019-07-24T00:00:00Z
date_updated: 2023-10-18T08:49:17Z
day: '24'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
doi: 10.15479/AT:ISTA:6891
file:
- access_level: closed
  checksum: 00d100d6468e31e583051e0a006b640c
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: akopf
  date_created: 2019-10-15T05:28:42Z
  date_updated: 2020-10-17T22:30:03Z
  embargo_to: open_access
  file_id: '6950'
  file_name: Kopf_PhD_Thesis.docx
  file_size: 74735267
  relation: source_file
- access_level: open_access
  checksum: 5d1baa899993ae6ca81aebebe1797000
  content_type: application/pdf
  creator: akopf
  date_created: 2019-10-15T05:28:47Z
  date_updated: 2020-10-17T22:30:03Z
  embargo: 2020-10-16
  file_id: '6951'
  file_name: Kopf_PhD_Thesis1.pdf
  file_size: 52787224
  relation: main_file
file_date_updated: 2020-10-17T22:30:03Z
has_accepted_license: '1'
keyword:
- cell biology
- immunology
- leukocyte
- migration
- microfluidics
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '171'
project:
- _id: 265E2996-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01250-B20
  name: Nano-Analytics of Cellular Systems
publication_identifier:
  eissn:
  - 2663-337X
  isbn:
  - 978-3-99078-002-2
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  link:
  - relation: press_release
    url: https://ist.ac.at/en/news/feeling-like-a-cell/
  record:
  - id: '6328'
    relation: part_of_dissertation
    status: public
  - id: '15'
    relation: part_of_dissertation
    status: public
  - id: '6877'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Michael K
  full_name: Sixt, Michael K
  id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
  last_name: Sixt
  orcid: 0000-0002-6620-9179
title: The implication of cytoskeletal dynamics on leukocyte migration
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...