---
OA_place: publisher
_id: '20149'
abstract:
- lang: eng
  text: "Immune responses depend on the coordinated and efficient migration of leukocytes.
    These\r\ncells, which are embedded and tightly confined within tissues, must navigate
    and traverse\r\ndiverse and complex three-dimensional environments. Leukocytes
    adapt their locomotory\r\nbehavior to the mechanical, geometrical, and biochemical
    characteristics of their\r\nsurroundings. In low-density environments, where the
    pore size of the interstitial matrix\r\nallows free passage, these cells position
    the nucleus directly behind the lamellipodium, the\r\nprotrusive actin structure
    that forms the leading front of the cell. In this configuration, they\r\nuse the
    nucleus as a gauge to identify the path of least resistance.\r\nHere, we show
    that in high-density environments, where the pore size precludes free passage\r\nof
    the cell body, leukocytes reposition the microtubule-organizing center (MTOC)
    and\r\nassociated organelles in front of the nucleus. In this configuration, they
    use actin structures\r\nprotruding orthogonally to the direction of migration
    in order to open a path for the cell body.\r\nWe identify two distinct actin populations
    that serve this purpose at different subcellular\r\nlocalizations. At the leading
    edge, local indentation of the plasma membrane leads to\r\nrecruitment of the
    Wiskott-Aldrich syndrome protein (WASp), which, via Arp2/3, results in\r\nthe
    formation of individual actin foci. At the cell body, actin polymerization is
    triggered by\r\nDOCK8, a Cdc42 exchange factor, resulting in the formation of
    a central actin pool.\r\nWe demonstrate that the central and peripheral actin
    pools are functionally communicating\r\nand that depletion of the central actin
    pool leads to increased actin accumulation at the cell\r\nfront, resulting in
    excessive extension of the leading edge."
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: NanoFab
acknowledgement: "I would like to acknowledge the\r\nfinancial support of the European
  Research Council through the ERC-SyG grant “Pushing from\r\nwithin: Control of cell
  shape, integrity and motility by cytoskeletal pushing forces”\r\n(01071793), which
  made this research possible. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Patricia
  full_name: Dos Reis Rodrigues, Patricia
  id: 26E95904-5160-11E9-9C0B-C5B0DC97E90F
  last_name: Dos Reis Rodrigues
  orcid: 0000-0003-1681-508X
citation:
  ama: Dos Reis Rodrigues P. Coordination of protrusive forces in immune cell migration
    . 2025. doi:<a href="https://doi.org/10.15479/AT-ISTA-20149">10.15479/AT-ISTA-20149</a>
  apa: Dos Reis Rodrigues, P. (2025). <i>Coordination of protrusive forces in immune
    cell migration </i>. Institute of Science and Technology Austria. <a href="https://doi.org/10.15479/AT-ISTA-20149">https://doi.org/10.15479/AT-ISTA-20149</a>
  chicago: Dos Reis Rodrigues, Patricia. “Coordination of Protrusive Forces in Immune
    Cell Migration .” Institute of Science and Technology Austria, 2025. <a href="https://doi.org/10.15479/AT-ISTA-20149">https://doi.org/10.15479/AT-ISTA-20149</a>.
  ieee: P. Dos Reis Rodrigues, “Coordination of protrusive forces in immune cell migration
    ,” Institute of Science and Technology Austria, 2025.
  ista: Dos Reis Rodrigues P. 2025. Coordination of protrusive forces in immune cell
    migration . Institute of Science and Technology Austria.
  mla: Dos Reis Rodrigues, Patricia. <i>Coordination of Protrusive Forces in Immune
    Cell Migration </i>. Institute of Science and Technology Austria, 2025, doi:<a
    href="https://doi.org/10.15479/AT-ISTA-20149">10.15479/AT-ISTA-20149</a>.
  short: P. Dos Reis Rodrigues, Coordination of Protrusive Forces in Immune Cell Migration
    , Institute of Science and Technology Austria, 2025.
corr_author: '1'
date_created: 2025-08-08T09:18:02Z
date_published: 2025-08-08T00:00:00Z
date_updated: 2026-04-28T13:26:50Z
day: '08'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MiSi
doi: 10.15479/AT-ISTA-20149
file:
- access_level: open_access
  checksum: fda8a1070667c3562263f4867609b41b
  content_type: application/pdf
  creator: prodrigu
  date_created: 2025-08-27T12:59:10Z
  date_updated: 2025-08-27T12:59:10Z
  file_id: '20232'
  file_name: 2025_ReisRodrigues_Patricia_Thesis.pdf
  file_size: 63885565
  relation: main_file
  success: 1
- access_level: closed
  checksum: e8b65affcbce846a926454df4b2867b9
  content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document
  creator: prodrigu
  date_created: 2025-08-27T13:00:30Z
  date_updated: 2025-08-27T13:02:28Z
  file_id: '20233'
  file_name: 2025_ReisRodrigues_Patricia_Thesis.docx
  file_size: 50483434
  relation: source_file
file_date_updated: 2025-08-27T13:02:28Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '08'
oa: 1
oa_version: Published Version
page: '114'
project:
- _id: bd91e723-d553-11ed-ba76-fe7eeb2185fd
  grant_number: '101071793'
  name: 'Pushing from within: Control of cell shape, integrity and motility by cytoskeletal
    pushing forces'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
  record:
  - id: '10703'
    relation: part_of_dissertation
    status: public
  - id: '20082'
    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: 'Coordination of protrusive forces in immune cell migration '
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2025'
...