---
OA_embargo: '6'
OA_place: publisher
_id: '19745'
abstract:
- lang: eng
  text: "Cell migration is a crucial process in animal development and maintenance.
    It is incredibly\r\nheterogeneous, with different cell types utilizing fundamentally
    distinct migration strategies.\r\nThe strategies also depend on the cellular microenvironment,
    where cells can switch between\r\nmigration modes as they encounter new environmental
    cues. In this thesis, we investigated\r\nhow dendritic cells adapt their migration
    strategy when encountering geometrically,\r\nmechanically and chemically distinct
    environments.\r\nWhen dendritic cells are embedded in a homogeneous fibrous network,
    they migrate in a fast\r\nand directional amoeboid manner. In this migration strategy,
    extracellular proteolysis and\r\nintegrin-mediated adhesions are dispensable.
    Instead, the cells use topography of the\r\nenvironment to propel their cell body
    forward. To migrate efficiently in the maze of different\r\npore sizes, they position
    the nucleus ahead of the microtubule organizing center (MTOC) and\r\nuse it to
    gauge the pores to identify the path of least resistance. Our aim was to identify\r\nwhether
    dendritic cells adapt their migration strategy when encountering asymmetrical\r\ntransitions
    into much denser environments with limited choice of large pores. In such invasive\r\ntransitions
    it is unclear if the cells can cross tight pores without the use of adhesions
    and\r\nextracellular proteolysis and whether they maintain the nucleus in the
    cell front.\r\nUsing various cell migration assays such as fibrous 3D collagen
    gels, geometrically defined\r\nmicrochannels with constrictions and simplistic
    under agarose migration assay, we provide\r\na comprehensive characterization
    of invasive migration of dendritic cells. We show that\r\nduring invasion the
    cells stall and stretch, reflecting the difficulty to translocate the bulky cell\r\nbody
    into the dense environment. In collagen gels, we show that dendritic cells can
    invade\r\nwithout proteolysis and adhesions. Instead, they utilize contractility,
    which can lead to largescale collagen compressions. During invasion, the nucleus
    stalls at tight constrictions, leading\r\nto a transient organelle reorientation.
    To resolve the stalling, upregulated rear contractility is\r\nrequired. This contractile
    force is simultaneously necessary for reverting the nucleus back to\r\nthe cell
    front after invasion and maintaining this positioning during permissive migration.\r\nA
    functional role of the reorientation was uncovered in the first collaboration
    project.\r\nA prominent central actin pool was identified around the MTOC, especially
    pronounced in\r\ndense and compressive environments. The actin pool was shown
    to generate pushing forces\r\nto dilate the space for cell translocation. These
    forces are only necessary in non-permissive\r\nenvironments, where the nucleus
    reorients to the cell rear, allowing the actin pool to\r\ngenerate space. In permissive
    environments where space generation is dispensable, the\r\nMTOC is located behind
    the nucleus and the actin cloud has reduced intensity, allowing more\r\nactin
    to be incorporated into the lamellipodium, speeding up migration.\r\nIn the second
    collaboration project, we investigated the effects of distinct chemical\r\nenvironments
    on dendritic cell migration. The strikingly persistent migration of these cells\r\nwas
    explained by their ability to modulate and even self-generate chemokine gradients.
    This\r\nallows the cells to migrate faster and more persistent in uniform chemokine
    fields compared\r\nto imposed chemokine gradients. The chemokine receptor CCR7
    was identified as a crucial\r\nplayer in this process, both sensing the signal
    and internalizing the chemokine to create a sink."
acknowledgement: "This project has received funding from the Austrian Science Fund
  (FWF) via the doctorate\r\ncollege DK NanoCell and from the European Union’s Horizon
  2020 research and innovation\r\nprogramme under the Marie Skłodowska-Curie Grant
  Agreement No. 665385.\r\n"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Nikola
  full_name: Canigova, Nikola
  id: 3795523E-F248-11E8-B48F-1D18A9856A87
  last_name: Canigova
  orcid: 0000-0002-8518-5926
citation:
  ama: Canigova N. Adaptive strategies of dendritic cell migration in response to
    environmental cues. 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-19745">10.15479/AT-ISTA-19745</a>
  apa: Canigova, N. (2025). <i>Adaptive strategies of dendritic cell migration in
    response to environmental cues</i>. Institute of Science and Technology Austria.
    <a href="https://doi.org/10.15479/AT-ISTA-19745">https://doi.org/10.15479/AT-ISTA-19745</a>
  chicago: Canigova, Nikola. “Adaptive Strategies of Dendritic Cell Migration in Response
    to Environmental Cues.” Institute of Science and Technology Austria, 2025. <a
    href="https://doi.org/10.15479/AT-ISTA-19745">https://doi.org/10.15479/AT-ISTA-19745</a>.
  ieee: N. Canigova, “Adaptive strategies of dendritic cell migration in response
    to environmental cues,” Institute of Science and Technology Austria, 2025.
  ista: Canigova N. 2025. Adaptive strategies of dendritic cell migration in response
    to environmental cues. Institute of Science and Technology Austria.
  mla: Canigova, Nikola. <i>Adaptive Strategies of Dendritic Cell Migration in Response
    to Environmental Cues</i>. Institute of Science and Technology Austria, 2025,
    doi:<a href="https://doi.org/10.15479/AT-ISTA-19745">10.15479/AT-ISTA-19745</a>.
  short: N. Canigova, Adaptive Strategies of Dendritic Cell Migration in Response
    to Environmental Cues, Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-05-26T08:49:00Z
date_published: 2025-05-27T00:00:00Z
date_updated: 2026-06-18T17:34:48Z
day: '27'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
- _id: GradSch
doi: 10.15479/AT-ISTA-19745
ec_funded: 1
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  date_created: 2025-05-28T07:38:17Z
  date_updated: 2025-11-27T23:30:02Z
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has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '133'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
- _id: 265E2996-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: W01250-B20
  name: Nano-Analytics of Cellular Systems
publication_identifier:
  isbn:
  - 978-3-99078-058-9
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '14274'
    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: Adaptive strategies of dendritic cell migration in response to environmental
  cues
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...