---
_id: '14360'
abstract:
- lang: eng
text: To navigate through diverse tissues, migrating cells must balance persistent
self-propelled motion with adaptive behaviors to circumvent obstacles. We identify
a curvature-sensing mechanism underlying obstacle evasion in immune-like cells.
Specifically, we propose that actin polymerization at the advancing edge of migrating
cells is inhibited by the curvature-sensitive BAR domain protein Snx33 in regions
with inward plasma membrane curvature. The genetic perturbation of this machinery
reduces the cells’ capacity to evade obstructions combined with faster and more
persistent cell migration in obstacle-free environments. Our results show how
cells can read out their surface topography and utilize actin and plasma membrane
biophysics to interpret their environment, allowing them to adaptively decide
if they should move ahead or turn away. On the basis of our findings, we propose
that the natural diversity of BAR domain proteins may allow cells to tune their
curvature sensing machinery to match the shape characteristics in their environment.
acknowledgement: "We thank Jan Ellenberg, Leanne Strauss, Anusha Gopalan, and Jia
Hui Li for critical feedback on the manuscript and the Life Science Editors for
editing assistance. The plasmid with hSnx33 was a kind gift from Duanqing Pei. Cell
line with GFP-tagged IRSp53 was a kind gift from Orion Weiner. We thank Brian Graziano
for providing protocols, reagents, and key advice to generate CRISPR knockout HL-60
cells. We thank the EMBL flow cytometry core facility, the EMBL advanced light microscopy
facility, the EMBL proteomics facility, and the EMBL genomics core facility for
support and advice. We thank Anusha Gopalan and Martin Bergert for their support
during mechanical measurements by AFM. We thank Estela Sosa Osorio for technical
assistance for the co-immunoprecipitation. We thank the EMBL genome biology computational
support (and specially Charles Girardot and Jelle Scholtalbers) for critical assistance
during RNAseq analysis. We thank Hans Kristian Hannibal‐Bach for his technical assistance
during the lipidomic analysis of plasma membrane isolates. We thank Steffen Burgold
for their support with LLS7 microscope in the ZEISS Microscopy Customer Center Europe.
We acknowledge the financial support of the European Molecular Biology Laboratory
(EMBL) to A.D.-M., Y.S., A.K., and A.E., the EMBL Interdisciplinary Postdocs (EIPOD)
program under Marie Sklodowska-Curie COFUND actions MSCA-COFUND-FP to M.S.B. and
M. S. (grant agreement number: 847543), the BEST program funding by FCT (SFRH/BEST/150300/2019)
to S.D.A. and the Joachim Herz Stiftung Add-on Fellowship for Interdisciplinary
Science to E.S.\r\nOpen Access funding enabled and organized by Projekt DEAL."
article_number: '5644'
article_processing_charge: Yes (via OA deal)
article_type: original
author:
- first_name: Ewa
full_name: Sitarska, Ewa
last_name: Sitarska
- first_name: Silvia Dias
full_name: Almeida, Silvia Dias
last_name: Almeida
- first_name: Marianne Sandvold
full_name: Beckwith, Marianne Sandvold
last_name: Beckwith
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Jakub
full_name: Czuchnowski, Jakub
last_name: Czuchnowski
- first_name: Marc
full_name: Siggel, Marc
last_name: Siggel
- first_name: Rita
full_name: Roessner, Rita
last_name: Roessner
- first_name: Aline
full_name: Tschanz, Aline
last_name: Tschanz
- first_name: Christer
full_name: Ejsing, Christer
last_name: Ejsing
- first_name: Yannick
full_name: Schwab, Yannick
last_name: Schwab
- first_name: Jan
full_name: Kosinski, Jan
last_name: Kosinski
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
- first_name: Anna
full_name: Kreshuk, Anna
last_name: Kreshuk
- first_name: Anna
full_name: Erzberger, Anna
last_name: Erzberger
- first_name: Alba
full_name: Diz-Muñoz, Alba
last_name: Diz-Muñoz
citation:
ama: Sitarska E, Almeida SD, Beckwith MS, et al. Sensing their plasma membrane curvature
allows migrating cells to circumvent obstacles. Nature Communications.
2023;14. doi:10.1038/s41467-023-41173-1
apa: Sitarska, E., Almeida, S. D., Beckwith, M. S., Stopp, J. A., Czuchnowski, J.,
Siggel, M., … Diz-Muñoz, A. (2023). Sensing their plasma membrane curvature allows
migrating cells to circumvent obstacles. Nature Communications. Springer
Nature. https://doi.org/10.1038/s41467-023-41173-1
chicago: Sitarska, Ewa, Silvia Dias Almeida, Marianne Sandvold Beckwith, Julian
A Stopp, Jakub Czuchnowski, Marc Siggel, Rita Roessner, et al. “Sensing Their
Plasma Membrane Curvature Allows Migrating Cells to Circumvent Obstacles.” Nature
Communications. Springer Nature, 2023. https://doi.org/10.1038/s41467-023-41173-1.
ieee: E. Sitarska et al., “Sensing their plasma membrane curvature allows
migrating cells to circumvent obstacles,” Nature Communications, vol. 14.
Springer Nature, 2023.
ista: Sitarska E, Almeida SD, Beckwith MS, Stopp JA, Czuchnowski J, Siggel M, Roessner
R, Tschanz A, Ejsing C, Schwab Y, Kosinski J, Sixt MK, Kreshuk A, Erzberger A,
Diz-Muñoz A. 2023. Sensing their plasma membrane curvature allows migrating cells
to circumvent obstacles. Nature Communications. 14, 5644.
mla: Sitarska, Ewa, et al. “Sensing Their Plasma Membrane Curvature Allows Migrating
Cells to Circumvent Obstacles.” Nature Communications, vol. 14, 5644, Springer
Nature, 2023, doi:10.1038/s41467-023-41173-1.
short: E. Sitarska, S.D. Almeida, M.S. Beckwith, J.A. Stopp, J. Czuchnowski, M.
Siggel, R. Roessner, A. Tschanz, C. Ejsing, Y. Schwab, J. Kosinski, M.K. Sixt,
A. Kreshuk, A. Erzberger, A. Diz-Muñoz, Nature Communications 14 (2023).
date_created: 2023-09-24T22:01:10Z
date_published: 2023-09-13T00:00:00Z
date_updated: 2023-12-21T14:30:01Z
day: '13'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1038/s41467-023-41173-1
external_id:
isi:
- '001087583700008'
pmid:
- '37704612'
file:
- access_level: open_access
checksum: ad670e3b3c64fc585675948370f6b149
content_type: application/pdf
creator: dernst
date_created: 2023-09-25T08:22:58Z
date_updated: 2023-09-25T08:22:58Z
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language:
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oa: 1
oa_version: Published Version
pmid: 1
publication: Nature Communications
publication_identifier:
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publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
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relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Sensing their plasma membrane curvature allows migrating cells to circumvent
obstacles
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2023'
...
---
_id: '14697'
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
citation:
ama: 'Stopp JA. Neutrophils on the hunt: Migratory strategies employed by neutrophils
to fulfill their effector function. 2023. doi:10.15479/at:ista:14697'
apa: 'Stopp, J. A. (2023). Neutrophils on the hunt: Migratory strategies employed
by neutrophils to fulfill their effector function. Institute of Science and
Technology Austria. https://doi.org/10.15479/at:ista:14697'
chicago: 'Stopp, Julian A. “Neutrophils on the Hunt: Migratory Strategies Employed
by Neutrophils to Fulfill Their Effector Function.” Institute of Science and Technology
Austria, 2023. https://doi.org/10.15479/at:ista:14697.'
ieee: 'J. A. Stopp, “Neutrophils on the hunt: Migratory strategies employed by neutrophils
to fulfill their effector function,” Institute of Science and Technology Austria,
2023.'
ista: 'Stopp JA. 2023. Neutrophils on the hunt: Migratory strategies employed by
neutrophils to fulfill their effector function. Institute of Science and Technology
Austria.'
mla: 'Stopp, Julian A. Neutrophils on the Hunt: Migratory Strategies Employed
by Neutrophils to Fulfill Their Effector Function. Institute of Science and
Technology Austria, 2023, doi:10.15479/at:ista:14697.'
short: 'J.A. Stopp, Neutrophils on the Hunt: Migratory Strategies Employed by Neutrophils
to Fulfill Their Effector Function, Institute of Science and Technology Austria,
2023.'
date_created: 2023-12-18T19:14:28Z
date_published: 2023-12-20T00:00:00Z
date_updated: 2023-12-21T14:30:02Z
day: '20'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: GradSch
- _id: MiSi
doi: 10.15479/at:ista:14697
ec_funded: 1
file:
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checksum: 457927165d5d556305d3086f6b83e5c7
content_type: application/pdf
creator: jstopp
date_created: 2023-12-20T09:35:34Z
date_updated: 2023-12-20T09:35:34Z
embargo: 2024-12-20
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file_id: '14699'
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creator: jstopp
date_created: 2023-12-20T09:35:35Z
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file_id: '14700'
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file_size: 69625950
relation: source_file
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has_accepted_license: '1'
language:
- iso: eng
month: '12'
oa_version: Published Version
page: '226'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
isbn:
- 978-3-99078-038-1
issn:
- 2663 - 337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '6328'
relation: part_of_dissertation
status: public
- id: '7885'
relation: part_of_dissertation
status: public
- id: '12272'
relation: part_of_dissertation
status: public
- id: '14274'
relation: part_of_dissertation
status: public
- id: '14360'
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: 'Neutrophils on the hunt: Migratory strategies employed by neutrophils to fulfill
their effector function'
type: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '14274'
abstract:
- lang: eng
text: Immune responses rely on the rapid and coordinated migration of leukocytes.
Whereas it is well established that single-cell migration is often guided by gradients
of chemokines and other chemoattractants, it remains poorly understood how these
gradients are generated, maintained, and modulated. By combining experimental
data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor
(GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor
that steers migration, CCR7 also acts as a generator and a modulator of chemotactic
gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively
internalize the receptor and ligand as part of the canonical GPCR desensitization
response. We show that CCR7 internalization also acts as an effective sink for
the chemoattractant, dynamically shaping the spatiotemporal distribution of the
chemokine. This mechanism drives complex collective migration patterns, enabling
DCs to create or sharpen chemotactic gradients. We further show that these self-generated
gradients can sustain the long-range guidance of DCs, adapt collective migration
patterns to the size and geometry of the environment, and provide a guidance cue
for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses
and consumes its ligand can thus provide a novel mode of cellular self-organization.
acknowledgement: "We thank I. de Vries and the Scientific Service Units (Life Sciences,
Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute
of Science and Technology Austria for excellent support, as well as all the rotation
students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis
work was supported by grants from the European Research Council under the European
Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant
agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20)
to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research
Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U.
was supported by the European Union’s Horizon 2020 research and innovation programme
under the Marie Skłodowska-Curie grant agreement no. 754411."
article_number: adc9584
article_processing_charge: No
article_type: original
author:
- first_name: Jonna H
full_name: Alanko, Jonna H
id: 2CC12E8C-F248-11E8-B48F-1D18A9856A87
last_name: Alanko
orcid: 0000-0002-7698-3061
- first_name: Mehmet C
full_name: Ucar, Mehmet C
id: 50B2A802-6007-11E9-A42B-EB23E6697425
last_name: Ucar
orcid: 0000-0003-0506-4217
- first_name: Nikola
full_name: Canigova, Nikola
id: 3795523E-F248-11E8-B48F-1D18A9856A87
last_name: Canigova
orcid: 0000-0002-8518-5926
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink
for CCL19 to coordinate collective leukocyte migration. Science Immunology.
2023;8(87). doi:10.1126/sciimmunol.adc9584
apa: Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin,
J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate
collective leukocyte migration. Science Immunology. American Association
for the Advancement of Science. https://doi.org/10.1126/sciimmunol.adc9584
chicago: Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz,
Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor
and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Science
Immunology. American Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciimmunol.adc9584.
ieee: J. H. Alanko et al., “CCR7 acts as both a sensor and a sink for CCL19
to coordinate collective leukocyte migration,” Science Immunology, vol.
8, no. 87. American Association for the Advancement of Science, 2023.
ista: Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB,
Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective
leukocyte migration. Science Immunology. 8(87), adc9584.
mla: Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to
Coordinate Collective Leukocyte Migration.” Science Immunology, vol. 8,
no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:10.1126/sciimmunol.adc9584.
short: J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B.
Hannezo, M.K. Sixt, Science Immunology 8 (2023).
date_created: 2023-09-06T08:07:51Z
date_published: 2023-09-01T00:00:00Z
date_updated: 2023-12-21T14:30:01Z
day: '01'
department:
- _id: MiSi
- _id: EdHa
- _id: NanoFab
doi: 10.1126/sciimmunol.adc9584
ec_funded: 1
external_id:
isi:
- '001062110600003'
pmid:
- '37656776'
intvolume: ' 8'
isi: 1
issue: '87'
keyword:
- General Medicine
- Immunology
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1126/sciimmunol.adc9584
month: '09'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 265E2996-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01250-B20
name: Nano-Analytics of Cellular Systems
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Science Immunology
publication_identifier:
issn:
- 2470-9468
publication_status: published
publisher: American Association for the Advancement of Science
quality_controlled: '1'
related_material:
record:
- id: '14279'
relation: research_data
status: public
- id: '14697'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte
migration
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 8
year: '2023'
...
---
_id: '12272'
abstract:
- lang: eng
text: Reading, interpreting and crawling along gradients of chemotactic cues is
one of the most complex questions in cell biology. In this issue, Georgantzoglou
et al. (2022. J. Cell. Biol.https://doi.org/10.1083/jcb.202103207) use in vivo
models to map the temporal sequence of how neutrophils respond to an acutely arising
gradient of chemoattractant.
article_number: e202206127
article_processing_charge: No
article_type: original
author:
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: 'Stopp JA, Sixt MK. Plan your trip before you leave: The neutrophils’ search-and-run
journey. Journal of Cell Biology. 2022;221(8). doi:10.1083/jcb.202206127'
apa: 'Stopp, J. A., & Sixt, M. K. (2022). Plan your trip before you leave: The
neutrophils’ search-and-run journey. Journal of Cell Biology. Rockefeller
University Press. https://doi.org/10.1083/jcb.202206127'
chicago: 'Stopp, Julian A, and Michael K Sixt. “Plan Your Trip before You Leave:
The Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology. Rockefeller
University Press, 2022. https://doi.org/10.1083/jcb.202206127.'
ieee: 'J. A. Stopp and M. K. Sixt, “Plan your trip before you leave: The neutrophils’
search-and-run journey,” Journal of Cell Biology, vol. 221, no. 8. Rockefeller
University Press, 2022.'
ista: 'Stopp JA, Sixt MK. 2022. Plan your trip before you leave: The neutrophils’
search-and-run journey. Journal of Cell Biology. 221(8), e202206127.'
mla: 'Stopp, Julian A., and Michael K. Sixt. “Plan Your Trip before You Leave: The
Neutrophils’ Search-and-Run Journey.” Journal of Cell Biology, vol. 221,
no. 8, e202206127, Rockefeller University Press, 2022, doi:10.1083/jcb.202206127.'
short: J.A. Stopp, M.K. Sixt, Journal of Cell Biology 221 (2022).
date_created: 2023-01-16T10:01:08Z
date_published: 2022-07-20T00:00:00Z
date_updated: 2023-12-21T14:30:01Z
day: '20'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1083/jcb.202206127
external_id:
isi:
- '000874717200001'
pmid:
- '35856919'
file:
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checksum: 6b1620743669679b48b9389bb40f5a11
content_type: application/pdf
creator: dernst
date_created: 2023-01-30T10:39:34Z
date_updated: 2023-01-30T10:39:34Z
file_id: '12451'
file_name: 2022_JourCellBiology_Stopp.pdf
file_size: 969969
relation: main_file
success: 1
file_date_updated: 2023-01-30T10:39:34Z
has_accepted_license: '1'
intvolume: ' 221'
isi: 1
issue: '8'
keyword:
- Cell Biology
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '07'
oa: 1
oa_version: Published Version
pmid: 1
publication: Journal of Cell Biology
publication_identifier:
eissn:
- 1540-8140
issn:
- 0021-9525
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
related_material:
record:
- id: '14697'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: 'Plan your trip before you leave: The neutrophils’ search-and-run journey'
tmp:
image: /images/cc_by_nc_sa.png
legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
BY-NC-SA 4.0)
short: CC BY-NC-SA (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 221
year: '2022'
...
---
_id: '7885'
abstract:
- lang: eng
text: Eukaryotic cells migrate by coupling the intracellular force of the actin
cytoskeleton to the environment. While force coupling is usually mediated by transmembrane
adhesion receptors, especially those of the integrin family, amoeboid cells such
as leukocytes can migrate extremely fast despite very low adhesive forces1. Here
we show that leukocytes cannot only migrate under low adhesion but can also transmit
forces in the complete absence of transmembrane force coupling. When confined
within three-dimensional environments, they use the topographical features of
the substrate to propel themselves. Here the retrograde flow of the actin cytoskeleton
follows the texture of the substrate, creating retrograde shear forces that are
sufficient to drive the cell body forwards. Notably, adhesion-dependent and adhesion-independent
migration are not mutually exclusive, but rather are variants of the same principle
of coupling retrograde actin flow to the environment and thus can potentially
operate interchangeably and simultaneously. As adhesion-free migration is independent
of the chemical composition of the environment, it renders cells completely autonomous
in their locomotive behaviour.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
acknowledgement: We thank A. Leithner and J. Renkawitz for discussion and critical
reading of the manuscript; J. Schwarz and M. Mehling for establishing the microfluidic
setups; the Bioimaging Facility of IST Austria for excellent support, as well as
the Life Science Facility and the Miba Machine Shop of IST Austria; and F. N. Arslan,
L. E. Burnett and L. Li for their work during their rotation in the IST PhD programme.
This work was supported by the European Research Council (ERC StG 281556 and CoG
724373) to M.S. and grants from the Austrian Science Fund (FWF P29911) and the WWTF
to M.S. M.H. was supported by the European Regional Development Fund Project (CZ.02.1.01/0.0/0.0/15_003/0000476).
F.G. received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant agreement no. 747687.
article_processing_charge: No
article_type: original
author:
- first_name: Anne
full_name: Reversat, Anne
id: 35B76592-F248-11E8-B48F-1D18A9856A87
last_name: Reversat
orcid: 0000-0003-0666-8928
- first_name: Florian R
full_name: Gärtner, Florian R
id: 397A88EE-F248-11E8-B48F-1D18A9856A87
last_name: Gärtner
orcid: 0000-0001-6120-3723
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Saren
full_name: Tasciyan, Saren
id: 4323B49C-F248-11E8-B48F-1D18A9856A87
last_name: Tasciyan
orcid: 0000-0003-1671-393X
- first_name: Juan L
full_name: Aguilera Servin, Juan L
id: 2A67C376-F248-11E8-B48F-1D18A9856A87
last_name: Aguilera Servin
orcid: 0000-0002-2862-8372
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Miroslav
full_name: Hons, Miroslav
id: 4167FE56-F248-11E8-B48F-1D18A9856A87
last_name: Hons
orcid: 0000-0002-6625-3348
- first_name: Matthieu
full_name: Piel, Matthieu
last_name: Piel
- first_name: Andrew
full_name: Callan-Jones, Andrew
last_name: Callan-Jones
- first_name: Raphael
full_name: Voituriez, Raphael
last_name: Voituriez
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Reversat A, Gärtner FR, Merrin J, et al. Cellular locomotion using environmental
topography. Nature. 2020;582:582–585. doi:10.1038/s41586-020-2283-z
apa: Reversat, A., Gärtner, F. R., Merrin, J., Stopp, J. A., Tasciyan, S., Aguilera
Servin, J. L., … Sixt, M. K. (2020). Cellular locomotion using environmental topography.
Nature. Springer Nature. https://doi.org/10.1038/s41586-020-2283-z
chicago: Reversat, Anne, Florian R Gärtner, Jack Merrin, Julian A Stopp, Saren Tasciyan,
Juan L Aguilera Servin, Ingrid de Vries, et al. “Cellular Locomotion Using Environmental
Topography.” Nature. Springer Nature, 2020. https://doi.org/10.1038/s41586-020-2283-z.
ieee: A. Reversat et al., “Cellular locomotion using environmental topography,”
Nature, vol. 582. Springer Nature, pp. 582–585, 2020.
ista: Reversat A, Gärtner FR, Merrin J, Stopp JA, Tasciyan S, Aguilera Servin JL,
de Vries I, Hauschild R, Hons M, Piel M, Callan-Jones A, Voituriez R, Sixt MK.
2020. Cellular locomotion using environmental topography. Nature. 582, 582–585.
mla: Reversat, Anne, et al. “Cellular Locomotion Using Environmental Topography.”
Nature, vol. 582, Springer Nature, 2020, pp. 582–585, doi:10.1038/s41586-020-2283-z.
short: A. Reversat, F.R. Gärtner, J. Merrin, J.A. Stopp, S. Tasciyan, J.L. Aguilera
Servin, I. de Vries, R. Hauschild, M. Hons, M. Piel, A. Callan-Jones, R. Voituriez,
M.K. Sixt, Nature 582 (2020) 582–585.
date_created: 2020-05-24T22:01:01Z
date_published: 2020-06-25T00:00:00Z
date_updated: 2024-03-25T23:30:12Z
day: '25'
department:
- _id: NanoFab
- _id: Bio
- _id: MiSi
doi: 10.1038/s41586-020-2283-z
ec_funded: 1
external_id:
isi:
- '000532688300008'
intvolume: ' 582'
isi: 1
language:
- iso: eng
month: '06'
oa_version: None
page: 582–585
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 26018E70-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P29911
name: Mechanical adaptation of lamellipodial actin
- _id: 260AA4E2-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '747687'
name: Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells
publication: Nature
publication_identifier:
eissn:
- '14764687'
issn:
- '00280836'
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/off-road-mode-enables-mobile-cells-to-move-freely/
record:
- id: '14697'
relation: dissertation_contains
status: public
- id: '12401'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Cellular locomotion using environmental topography
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 582
year: '2020'
...
---
_id: '6328'
abstract:
- lang: eng
text: During metazoan development, immune surveillance and cancer dissemination,
cells migrate in complex three-dimensional microenvironments1,2,3. These spaces
are crowded by cells and extracellular matrix, generating mazes with differently
sized gaps that are typically smaller than the diameter of the migrating cell4,5.
Most mesenchymal and epithelial cells and some—but not all—cancer cells actively
generate their migratory path using pericellular tissue proteolysis6. By contrast,
amoeboid cells such as leukocytes use non-destructive strategies of locomotion7,
raising the question how these extremely fast cells navigate through dense tissues.
Here we reveal that leukocytes sample their immediate vicinity for large pore
sizes, and are thereby able to choose the path of least resistance. This allows
them to circumnavigate local obstacles while effectively following global directional
cues such as chemotactic gradients. Pore-size discrimination is facilitated by
frontward positioning of the nucleus, which enables the cells to use their bulkiest
compartment as a mechanical gauge. Once the nucleus and the closely associated
microtubule organizing centre pass the largest pore, cytoplasmic protrusions still
lingering in smaller pores are retracted. These retractions are coordinated by
dynamic microtubules; when microtubules are disrupted, migrating cells lose coherence
and frequently fragment into migratory cytoplasmic pieces. As nuclear positioning
in front of the microtubule organizing centre is a typical feature of amoeboid
migration, our findings link the fundamental organization of cellular polarity
to the strategy of locomotion.
acknowledged_ssus:
- _id: SSU
article_processing_charge: No
article_type: letter_note
author:
- first_name: Jörg
full_name: Renkawitz, Jörg
id: 3F0587C8-F248-11E8-B48F-1D18A9856A87
last_name: Renkawitz
orcid: 0000-0003-2856-3369
- first_name: Aglaja
full_name: Kopf, Aglaja
id: 31DAC7B6-F248-11E8-B48F-1D18A9856A87
last_name: Kopf
orcid: 0000-0002-2187-6656
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Ingrid
full_name: de Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: de Vries
- first_name: Meghan K.
full_name: Driscoll, Meghan K.
last_name: Driscoll
- first_name: Jack
full_name: Merrin, Jack
id: 4515C308-F248-11E8-B48F-1D18A9856A87
last_name: Merrin
orcid: 0000-0001-5145-4609
- first_name: Robert
full_name: Hauschild, Robert
id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
last_name: Hauschild
orcid: 0000-0001-9843-3522
- first_name: Erik S.
full_name: Welf, Erik S.
last_name: Welf
- first_name: Gaudenz
full_name: Danuser, Gaudenz
last_name: Danuser
- first_name: Reto
full_name: Fiolka, Reto
last_name: Fiolka
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Renkawitz J, Kopf A, Stopp JA, et al. Nuclear positioning facilitates amoeboid
migration along the path of least resistance. Nature. 2019;568:546-550.
doi:10.1038/s41586-019-1087-5
apa: Renkawitz, J., Kopf, A., Stopp, J. A., de Vries, I., Driscoll, M. K., Merrin,
J., … Sixt, M. K. (2019). Nuclear positioning facilitates amoeboid migration along
the path of least resistance. Nature. Springer Nature. https://doi.org/10.1038/s41586-019-1087-5
chicago: Renkawitz, Jörg, Aglaja Kopf, Julian A Stopp, Ingrid de Vries, Meghan K.
Driscoll, Jack Merrin, Robert Hauschild, et al. “Nuclear Positioning Facilitates
Amoeboid Migration along the Path of Least Resistance.” Nature. Springer
Nature, 2019. https://doi.org/10.1038/s41586-019-1087-5.
ieee: J. Renkawitz et al., “Nuclear positioning facilitates amoeboid migration
along the path of least resistance,” Nature, vol. 568. Springer Nature,
pp. 546–550, 2019.
ista: Renkawitz J, Kopf A, Stopp JA, de Vries I, Driscoll MK, Merrin J, Hauschild
R, Welf ES, Danuser G, Fiolka R, Sixt MK. 2019. Nuclear positioning facilitates
amoeboid migration along the path of least resistance. Nature. 568, 546–550.
mla: Renkawitz, Jörg, et al. “Nuclear Positioning Facilitates Amoeboid Migration
along the Path of Least Resistance.” Nature, vol. 568, Springer Nature,
2019, pp. 546–50, doi:10.1038/s41586-019-1087-5.
short: J. Renkawitz, A. Kopf, J.A. Stopp, I. de Vries, M.K. Driscoll, J. Merrin,
R. Hauschild, E.S. Welf, G. Danuser, R. Fiolka, M.K. Sixt, Nature 568 (2019) 546–550.
date_created: 2019-04-17T06:52:28Z
date_published: 2019-04-25T00:00:00Z
date_updated: 2024-03-25T23:30:22Z
day: '25'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
doi: 10.1038/s41586-019-1087-5
ec_funded: 1
external_id:
isi:
- '000465594200050'
pmid:
- '30944468'
intvolume: ' 568'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217284/
month: '04'
oa: 1
oa_version: Submitted Version
page: 546-550
pmid: 1
project:
- _id: 25A603A2-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '281556'
name: Cytoskeletal force generation and force transduction of migrating leukocytes
(EU)
- _id: 25FE9508-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '724373'
name: Cellular navigation along spatial gradients
- _id: 265FAEBA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W01250-B20
name: Nano-Analytics of Cellular Systems
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25A48D24-B435-11E9-9278-68D0E5697425
grant_number: ALTF 1396-2014
name: Molecular and system level view of immune cell migration
publication: Nature
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/leukocytes-use-their-nucleus-as-a-ruler-to-choose-path-of-least-resistance/
record:
- id: '14697'
relation: dissertation_contains
status: public
- id: '6891'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Nuclear positioning facilitates amoeboid migration along the path of least
resistance
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 568
year: '2019'
...
---
_id: '6059'
abstract:
- lang: eng
text: Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis
and/or NETosis. Apartfrom these conventional roles, PMN also have immune-regulatory
functions. They can transdifferentiateand upregulate MHCII as well as ligands
for costimulatory receptors which enables them to behave asantigen presenting
cells (APC). The initial step for activating T-cells is the formation of an immunesynapse
between T-cells and antigen-presenting cells. However, the immune synapse that
develops atthe PMN/T-cell contact zone is as yet hardly investigated due to the
non-availability of methods foranalysis of large number of PMN interactions. In
order to overcome these obstacles, we introduce herea workflow to analyse the
immune synapse of primary human PMN and T-cells using multispectral imag-ing flow
cytometry (InFlow microscopy) and super-resolution microscopy. For that purpose,
we used CD3and CD66b as the lineage markers for T-cells and PMN, respectively.
Thereafter, we applied and criticallydiscussed various ‘‘masks” for identification
of T-cell PMN interactions. Using this approach, we foundthat a small fraction
of transdifferentiated PMN (CD66b+CD86high) formed stable PMN/T-cell conjugates.Interestingly,
while both CD3 and CD66b accumulation in the immune synapse was dependent on thematuration
state of the PMN, only CD3 accumulation was greatly enhanced by the presence of
superanti-gen. The actin cytoskeleton was weakly rearranged at the PMN side on
the immune synapse upon contactwith a T-cell in the presence of superantigen.
A more detailed analysis using super-resolution microscopy(structured-illumination
microscopy, SIM) confirmed this finding. Together, we present an InFlow micro-scopy
based approach for the large scale analysis of PMN/T-cell interactions and – combined
with SIM – apossibility for an in-depth analysis of protein translocation at the
site of interactions.
author:
- first_name: Emre
full_name: Balta, Emre
last_name: Balta
- first_name: Julian A
full_name: Stopp, Julian A
id: 489E3F00-F248-11E8-B48F-1D18A9856A87
last_name: Stopp
- first_name: Laura
full_name: Castelletti, Laura
last_name: Castelletti
- first_name: Henning
full_name: Kirchgessner, Henning
last_name: Kirchgessner
- first_name: Yvonne
full_name: Samstag, Yvonne
last_name: Samstag
- first_name: Guido H.
full_name: Wabnitz, Guido H.
last_name: Wabnitz
citation:
ama: Balta E, Stopp JA, Castelletti L, Kirchgessner H, Samstag Y, Wabnitz GH. Qualitative
and quantitative analysis of PMN/T-cell interactions by InFlow and super-resolution
microscopy. Methods. 2017;112(1):25-38. doi:10.1016/j.ymeth.2016.09.013
apa: Balta, E., Stopp, J. A., Castelletti, L., Kirchgessner, H., Samstag, Y., &
Wabnitz, G. H. (2017). Qualitative and quantitative analysis of PMN/T-cell interactions
by InFlow and super-resolution microscopy. Methods. Elsevier. https://doi.org/10.1016/j.ymeth.2016.09.013
chicago: Balta, Emre, Julian A Stopp, Laura Castelletti, Henning Kirchgessner, Yvonne
Samstag, and Guido H. Wabnitz. “Qualitative and Quantitative Analysis of PMN/T-Cell
Interactions by InFlow and Super-Resolution Microscopy.” Methods. Elsevier,
2017. https://doi.org/10.1016/j.ymeth.2016.09.013.
ieee: E. Balta, J. A. Stopp, L. Castelletti, H. Kirchgessner, Y. Samstag, and G.
H. Wabnitz, “Qualitative and quantitative analysis of PMN/T-cell interactions
by InFlow and super-resolution microscopy,” Methods, vol. 112, no. 1. Elsevier,
pp. 25–38, 2017.
ista: Balta E, Stopp JA, Castelletti L, Kirchgessner H, Samstag Y, Wabnitz GH. 2017.
Qualitative and quantitative analysis of PMN/T-cell interactions by InFlow and
super-resolution microscopy. Methods. 112(1), 25–38.
mla: Balta, Emre, et al. “Qualitative and Quantitative Analysis of PMN/T-Cell Interactions
by InFlow and Super-Resolution Microscopy.” Methods, vol. 112, no. 1, Elsevier,
2017, pp. 25–38, doi:10.1016/j.ymeth.2016.09.013.
short: E. Balta, J.A. Stopp, L. Castelletti, H. Kirchgessner, Y. Samstag, G.H. Wabnitz,
Methods 112 (2017) 25–38.
date_created: 2019-02-26T13:45:17Z
date_published: 2017-01-01T00:00:00Z
date_updated: 2021-01-12T08:05:57Z
day: '01'
doi: 10.1016/j.ymeth.2016.09.013
extern: '1'
external_id:
pmid:
- '27693880'
intvolume: ' 112'
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: 25-38
pmid: 1
publication: Methods
publication_identifier:
issn:
- 1046-2023
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
link:
- relation: supplementary_material
url: http://dx.doi.org/10.1016/j.ymeth.2016.09.013
status: public
title: Qualitative and quantitative analysis of PMN/T-cell interactions by InFlow
and super-resolution microscopy
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2017'
...