---
_id: '1285'
abstract:
- lang: eng
text: Cell migration is central to a multitude of physiological processes, including
embryonic development, immune surveillance, and wound healing, and deregulated
migration is key to cancer dissemination. Decades of investigations have uncovered
many of the molecular and physical mechanisms underlying cell migration. Together
with protrusion extension and cell body retraction, adhesion to the substrate
via specific focal adhesion points has long been considered an essential step
in cell migration. Although this is true for cells moving on two-dimensional substrates,
recent studies have demonstrated that focal adhesions are not required for cells
moving in three dimensions, in which confinement is sufficient to maintain a cell
in contact with its substrate. Here, we review the investigations that have led
to challenging the requirement of specific adhesions for migration, discuss the
physical mechanisms proposed for cell body translocation during focal adhesion-independent
migration, and highlight the remaining open questions for the future.
acknowledgement: We would like to thank Dani Bodor for critical comments on the manuscript
and Guillaume Salbreux for discussions. The authors are supported by the United
Kingdom's Medical Research Council (MRC) (E.K.P. and I.M.A.; core funding to the
MRC Laboratory for Molecular Cell Biology), by the European Research Council [ERC
GA 311637 (E.K.P.) and ERC GA 281556 (M.S.)], and by a START award from the Austrian
Science Foundation (M.S.).
author:
- first_name: Ewa
full_name: Paluch, Ewa
last_name: Paluch
- first_name: Irene
full_name: Aspalter, Irene
last_name: Aspalter
- 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: Paluch E, Aspalter I, Sixt MK. Focal adhesion-independent cell migration. Annual
Review of Cell and Developmental Biology. 2016;32:469-490. doi:10.1146/annurev-cellbio-111315-125341
apa: Paluch, E., Aspalter, I., & Sixt, M. K. (2016). Focal adhesion-independent
cell migration. Annual Review of Cell and Developmental Biology. Annual
Reviews. https://doi.org/10.1146/annurev-cellbio-111315-125341
chicago: Paluch, Ewa, Irene Aspalter, and Michael K Sixt. “Focal Adhesion-Independent
Cell Migration.” Annual Review of Cell and Developmental Biology. Annual
Reviews, 2016. https://doi.org/10.1146/annurev-cellbio-111315-125341.
ieee: E. Paluch, I. Aspalter, and M. K. Sixt, “Focal adhesion-independent cell migration,”
Annual Review of Cell and Developmental Biology, vol. 32. Annual Reviews,
pp. 469–490, 2016.
ista: Paluch E, Aspalter I, Sixt MK. 2016. Focal adhesion-independent cell migration.
Annual Review of Cell and Developmental Biology. 32, 469–490.
mla: Paluch, Ewa, et al. “Focal Adhesion-Independent Cell Migration.” Annual
Review of Cell and Developmental Biology, vol. 32, Annual Reviews, 2016, pp.
469–90, doi:10.1146/annurev-cellbio-111315-125341.
short: E. Paluch, I. Aspalter, M.K. Sixt, Annual Review of Cell and Developmental
Biology 32 (2016) 469–490.
date_created: 2018-12-11T11:51:08Z
date_published: 2016-10-06T00:00:00Z
date_updated: 2021-01-12T06:49:37Z
day: '06'
department:
- _id: MiSi
doi: 10.1146/annurev-cellbio-111315-125341
ec_funded: 1
intvolume: ' 32'
language:
- iso: eng
month: '10'
oa_version: None
page: 469 - 490
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: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Annual Review of Cell and Developmental Biology
publication_status: published
publisher: Annual Reviews
publist_id: '6031'
quality_controlled: '1'
scopus_import: 1
status: public
title: Focal adhesion-independent cell migration
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 32
year: '2016'
...
---
_id: '1490'
abstract:
- lang: eng
text: To induce adaptive immunity, dendritic cells (DCs) migrate through afferent
lymphatic vessels (LVs) to draining lymph nodes (dLNs). This process occurs in
several consecutive steps. Upon entry into lymphatic capillaries, DCs first actively
crawl into downstream collecting vessels. From there, they are next passively
and rapidly transported to the dLN by lymph flow. Here, we describe a role for
the chemokine CCL21 in intralymphatic DC crawling. Performing time-lapse imaging
in murine skin, we found that blockade of CCL21-but not the absence of lymph flow-completely
abolished DC migration from capillaries toward collecting vessels and reduced
the ability of intralymphatic DCs to emigrate from skin. Moreover, we found that
in vitro low laminar flow established a CCL21 gradient along lymphatic endothelial
monolayers, thereby inducing downstream-directed DC migration. These findings
reveal a role for intralymphatic CCL21 in promoting DC trafficking to dLNs, through
the formation of a flow-induced gradient.
author:
- first_name: Erica
full_name: Russo, Erica
last_name: Russo
- first_name: Alvaro
full_name: Teijeira, Alvaro
last_name: Teijeira
- first_name: Kari
full_name: Vaahtomeri, Kari
id: 368EE576-F248-11E8-B48F-1D18A9856A87
last_name: Vaahtomeri
orcid: 0000-0001-7829-3518
- first_name: Ann
full_name: Willrodt, Ann
last_name: Willrodt
- first_name: Joël
full_name: Bloch, Joël
last_name: Bloch
- first_name: Maximilian
full_name: Nitschké, Maximilian
last_name: Nitschké
- first_name: Laura
full_name: Santambrogio, Laura
last_name: Santambrogio
- first_name: Dontscho
full_name: Kerjaschki, Dontscho
last_name: Kerjaschki
- 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: Cornelia
full_name: Halin, Cornelia
last_name: Halin
citation:
ama: Russo E, Teijeira A, Vaahtomeri K, et al. Intralymphatic CCL21 promotes tissue
egress of dendritic cells through afferent lymphatic vessels. Cell Reports.
2016;14(7):1723-1734. doi:10.1016/j.celrep.2016.01.048
apa: Russo, E., Teijeira, A., Vaahtomeri, K., Willrodt, A., Bloch, J., Nitschké,
M., … Halin, C. (2016). Intralymphatic CCL21 promotes tissue egress of dendritic
cells through afferent lymphatic vessels. Cell Reports. Cell Press. https://doi.org/10.1016/j.celrep.2016.01.048
chicago: Russo, Erica, Alvaro Teijeira, Kari Vaahtomeri, Ann Willrodt, Joël Bloch,
Maximilian Nitschké, Laura Santambrogio, Dontscho Kerjaschki, Michael K Sixt,
and Cornelia Halin. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic
Cells through Afferent Lymphatic Vessels.” Cell Reports. Cell Press, 2016.
https://doi.org/10.1016/j.celrep.2016.01.048.
ieee: E. Russo et al., “Intralymphatic CCL21 promotes tissue egress of dendritic
cells through afferent lymphatic vessels,” Cell Reports, vol. 14, no. 7.
Cell Press, pp. 1723–1734, 2016.
ista: Russo E, Teijeira A, Vaahtomeri K, Willrodt A, Bloch J, Nitschké M, Santambrogio
L, Kerjaschki D, Sixt MK, Halin C. 2016. Intralymphatic CCL21 promotes tissue
egress of dendritic cells through afferent lymphatic vessels. Cell Reports. 14(7),
1723–1734.
mla: Russo, Erica, et al. “Intralymphatic CCL21 Promotes Tissue Egress of Dendritic
Cells through Afferent Lymphatic Vessels.” Cell Reports, vol. 14, no. 7,
Cell Press, 2016, pp. 1723–34, doi:10.1016/j.celrep.2016.01.048.
short: E. Russo, A. Teijeira, K. Vaahtomeri, A. Willrodt, J. Bloch, M. Nitschké,
L. Santambrogio, D. Kerjaschki, M.K. Sixt, C. Halin, Cell Reports 14 (2016) 1723–1734.
date_created: 2018-12-11T11:52:19Z
date_published: 2016-02-23T00:00:00Z
date_updated: 2021-01-12T06:51:07Z
day: '23'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.1016/j.celrep.2016.01.048
file:
- access_level: open_access
checksum: c98c1151d5f1e5ce1643a83d8d7f3c29
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:30Z
date_updated: 2020-07-14T12:44:58Z
file_id: '4948'
file_name: IST-2016-515-v1+1_1-s2.0-S2211124716300262-main.pdf
file_size: 5489897
relation: main_file
file_date_updated: 2020-07-14T12:44:58Z
has_accepted_license: '1'
intvolume: ' 14'
issue: '7'
language:
- iso: eng
month: '02'
oa: 1
oa_version: Published Version
page: 1723 - 1734
publication: Cell Reports
publication_status: published
publisher: Cell Press
publist_id: '5697'
pubrep_id: '515'
quality_controlled: '1'
scopus_import: 1
status: public
title: Intralymphatic CCL21 promotes tissue egress of dendritic cells through afferent
lymphatic vessels
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: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 14
year: '2016'
...
---
_id: '1599'
abstract:
- lang: eng
text: "The addition of polysialic acid to N- and/or O-linked glycans, referred to
as polysialylation, is a rare posttranslational modification that is mainly known
to control the developmental plasticity of the nervous system. Here we show that
CCR7, the central chemokine receptor controlling immune cell trafficking to secondary
lymphatic organs, carries polysialic acid. This modification is essential for
the recognition of the CCR7 ligand CCL21. As a consequence, dendritic cell trafficking
is abrogated in polysialyltransferase-deficient mice, manifesting as disturbed
lymph node homeostasis and unresponsiveness to inflammatory stimuli. Structure-function
analysis of chemokine-receptor interactions reveals that CCL21 adopts an autoinhibited
conformation, which is released upon interaction with polysialic acid. Thus, we
describe a glycosylation-mediated immune cell trafficking disorder and its mechanistic
basis.\r\n"
acknowledged_ssus:
- _id: SSU
acknowledgement: 'We thank S. Schüchner and E. Ogris for kindly providing the antibody
to GFP, M. Helmbrecht and A. Huber for providing Nrp2−/− mice, the IST Scientific
Support Facilities for excellent services, and J. Renkawitz and K. Vaahtomeri for
critically reading the manuscript. '
article_processing_charge: No
article_type: original
author:
- first_name: Eva
full_name: Kiermaier, Eva
id: 3EB04B78-F248-11E8-B48F-1D18A9856A87
last_name: Kiermaier
orcid: 0000-0001-6165-5738
- first_name: Christine
full_name: Moussion, Christine
id: 3356F664-F248-11E8-B48F-1D18A9856A87
last_name: Moussion
- first_name: Christopher
full_name: Veldkamp, Christopher
last_name: Veldkamp
- first_name: Rita
full_name: Gerardy Schahn, Rita
last_name: Gerardy Schahn
- first_name: Ingrid
full_name: De Vries, Ingrid
id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
last_name: De Vries
- first_name: Larry
full_name: Williams, Larry
last_name: Williams
- first_name: Gary
full_name: Chaffee, Gary
last_name: Chaffee
- first_name: Andrew
full_name: Phillips, Andrew
last_name: Phillips
- first_name: Friedrich
full_name: Freiberger, Friedrich
last_name: Freiberger
- first_name: Richard
full_name: Imre, Richard
last_name: Imre
- first_name: Deni
full_name: Taleski, Deni
last_name: Taleski
- first_name: Richard
full_name: Payne, Richard
last_name: Payne
- first_name: Asolina
full_name: Braun, Asolina
last_name: Braun
- first_name: Reinhold
full_name: Förster, Reinhold
last_name: Förster
- first_name: Karl
full_name: Mechtler, Karl
last_name: Mechtler
- first_name: Martina
full_name: Mühlenhoff, Martina
last_name: Mühlenhoff
- first_name: Brian
full_name: Volkman, Brian
last_name: Volkman
- 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: Kiermaier E, Moussion C, Veldkamp C, et al. Polysialylation controls dendritic
cell trafficking by regulating chemokine recognition. Science. 2016;351(6269):186-190.
doi:10.1126/science.aad0512
apa: Kiermaier, E., Moussion, C., Veldkamp, C., Gerardy Schahn, R., de Vries, I.,
Williams, L., … Sixt, M. K. (2016). Polysialylation controls dendritic cell trafficking
by regulating chemokine recognition. Science. American Association for
the Advancement of Science. https://doi.org/10.1126/science.aad0512
chicago: Kiermaier, Eva, Christine Moussion, Christopher Veldkamp, Rita Gerardy
Schahn, Ingrid de Vries, Larry Williams, Gary Chaffee, et al. “Polysialylation
Controls Dendritic Cell Trafficking by Regulating Chemokine Recognition.” Science.
American Association for the Advancement of Science, 2016. https://doi.org/10.1126/science.aad0512.
ieee: E. Kiermaier et al., “Polysialylation controls dendritic cell trafficking
by regulating chemokine recognition,” Science, vol. 351, no. 6269. American
Association for the Advancement of Science, pp. 186–190, 2016.
ista: Kiermaier E, Moussion C, Veldkamp C, Gerardy Schahn R, de Vries I, Williams
L, Chaffee G, Phillips A, Freiberger F, Imre R, Taleski D, Payne R, Braun A, Förster
R, Mechtler K, Mühlenhoff M, Volkman B, Sixt MK. 2016. Polysialylation controls
dendritic cell trafficking by regulating chemokine recognition. Science. 351(6269),
186–190.
mla: Kiermaier, Eva, et al. “Polysialylation Controls Dendritic Cell Trafficking
by Regulating Chemokine Recognition.” Science, vol. 351, no. 6269, American
Association for the Advancement of Science, 2016, pp. 186–90, doi:10.1126/science.aad0512.
short: E. Kiermaier, C. Moussion, C. Veldkamp, R. Gerardy Schahn, I. de Vries,
L. Williams, G. Chaffee, A. Phillips, F. Freiberger, R. Imre, D. Taleski, R. Payne,
A. Braun, R. Förster, K. Mechtler, M. Mühlenhoff, B. Volkman, M.K. Sixt, Science
351 (2016) 186–190.
date_created: 2018-12-11T11:52:57Z
date_published: 2016-01-08T00:00:00Z
date_updated: 2021-01-12T06:51:52Z
day: '08'
department:
- _id: MiSi
doi: 10.1126/science.aad0512
ec_funded: 1
external_id:
pmid:
- '26657283'
intvolume: ' 351'
issue: '6269'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583642/
month: '01'
oa: 1
oa_version: Submitted Version
page: 186 - 190
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: 25A76F58-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '289720'
name: Stromal Cell-immune Cell Interactions in Health and Disease
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '5570'
quality_controlled: '1'
scopus_import: 1
status: public
title: Polysialylation controls dendritic cell trafficking by regulating chemokine
recognition
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 351
year: '2016'
...
---
_id: '1597'
abstract:
- lang: eng
text: Chemokines are the main guidance cues directing leukocyte migration. Opposed
to early assumptions, chemokines do not necessarily act as soluble cues but are
often immobilized within tissues, e.g., dendritic cell migration toward lymphatic
vessels is guided by a haptotactic gradient of the chemokine CCL21. Controlled
assay systems to quantitatively study haptotaxis in vitro are still missing. In
this chapter, we describe an in vitro haptotaxis assay optimized for the unique
properties of dendritic cells. The chemokine CCL21 is immobilized in a bioactive
state, using laser-assisted protein adsorption by photobleaching. The cells follow
this immobilized CCL21 gradient in a haptotaxis chamber, which provides three
dimensionally confined migration conditions.
acknowledged_ssus:
- _id: Bio
acknowledgement: This work was supported by the Boehringer Ingelheim Fonds, the European
Research Council (ERC StG 281556), and a START Award of the Austrian Science Foundation
(FWF). We thank Robert Hauschild, Anne Reversat, and Jack Merrin for valuable input
and the Imaging Facility of IST Austria for excellent support.
article_processing_charge: No
article_type: original
author:
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
- 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: Schwarz J, Sixt MK. Quantitative analysis of dendritic cell haptotaxis. Methods
in Enzymology. 2016;570:567-581. doi:10.1016/bs.mie.2015.11.004
apa: Schwarz, J., & Sixt, M. K. (2016). Quantitative analysis of dendritic cell
haptotaxis. Methods in Enzymology. Elsevier. https://doi.org/10.1016/bs.mie.2015.11.004
chicago: Schwarz, Jan, and Michael K Sixt. “Quantitative Analysis of Dendritic Cell
Haptotaxis.” Methods in Enzymology. Elsevier, 2016. https://doi.org/10.1016/bs.mie.2015.11.004.
ieee: J. Schwarz and M. K. Sixt, “Quantitative analysis of dendritic cell haptotaxis,”
Methods in Enzymology, vol. 570. Elsevier, pp. 567–581, 2016.
ista: Schwarz J, Sixt MK. 2016. Quantitative analysis of dendritic cell haptotaxis.
Methods in Enzymology. 570, 567–581.
mla: Schwarz, Jan, and Michael K. Sixt. “Quantitative Analysis of Dendritic Cell
Haptotaxis.” Methods in Enzymology, vol. 570, Elsevier, 2016, pp. 567–81,
doi:10.1016/bs.mie.2015.11.004.
short: J. Schwarz, M.K. Sixt, Methods in Enzymology 570 (2016) 567–581.
date_created: 2018-12-11T11:52:56Z
date_published: 2016-01-01T00:00:00Z
date_updated: 2021-01-12T06:51:51Z
day: '01'
department:
- _id: MiSi
doi: 10.1016/bs.mie.2015.11.004
ec_funded: 1
external_id:
pmid:
- '26921962'
intvolume: ' 570'
language:
- iso: eng
month: '01'
oa_version: None
page: 567 - 581
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: 25A8E5EA-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Y 564-B12
name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Methods in Enzymology
publication_status: published
publisher: Elsevier
publist_id: '5573'
quality_controlled: '1'
scopus_import: 1
status: public
title: Quantitative analysis of dendritic cell haptotaxis
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 570
year: '2016'
...
---
_id: '1129'
abstract:
- lang: eng
text: "Directed cell migration is a hallmark feature, present in almost all multi-cellular\r\norganisms.
Despite its importance, basic questions regarding force transduction\r\nor directional
sensing are still heavily investigated. Directed migration of cells\r\nguided
by immobilized guidance cues - haptotaxis - occurs in key-processes,\r\nsuch as
embryonic development and immunity (Middleton et al., 1997; Nguyen\r\net al.,
2000; Thiery, 1984; Weber et al., 2013). Immobilized guidance cues\r\ncomprise
adhesive ligands, such as collagen and fibronectin (Barczyk et al.,\r\n2009),
or chemokines - the main guidance cues for migratory leukocytes\r\n(Middleton
et al., 1997; Weber et al., 2013). While adhesive ligands serve as\r\nattachment
sites guiding cell migration (Carter, 1965), chemokines instruct\r\nhaptotactic
migration by inducing adhesion to adhesive ligands and directional\r\nguidance
(Rot and Andrian, 2004; Schumann et al., 2010). Quantitative analysis\r\nof the
cellular response to immobilized guidance cues requires in vitro assays\r\nthat
foster cell migration, offer accurate control of the immobilized cues on a\r\nsubcellular
scale and in the ideal case closely reproduce in vivo conditions. The\r\nexploration
of haptotactic cell migration through design and employment of such\r\nassays
represents the main focus of this work.\r\nDendritic cells (DCs) are leukocytes,
which after encountering danger\r\nsignals such as pathogens in peripheral organs
instruct naïve T-cells and\r\nconsequently the adaptive immune response in the
lymph node (Mellman and\r\nSteinman, 2001). To reach the lymph node from the periphery,
DCs follow\r\nhaptotactic gradients of the chemokine CCL21 towards lymphatic vessels\r\n(Weber
et al., 2013). Questions about how DCs interpret haptotactic CCL21\r\ngradients
have not yet been addressed. The main reason for this is the lack of\r\nan assay
that offers diverse haptotactic environments, hence allowing the study\r\nof DC
migration as a response to different signals of immobilized guidance cue.\r\nIn
this work, we developed an in vitro assay that enables us to\r\nquantitatively
assess DC haptotaxis, by combining precisely controllable\r\nchemokine photo-patterning
with physically confining migration conditions. With this tool at hand, we studied
the influence of CCL21 gradient properties and\r\nconcentration on DC haptotaxis.
We found that haptotactic gradient sensing\r\ndepends on the absolute CCL21 concentration
in combination with the local\r\nsteepness of the gradient. Our analysis suggests
that the directionality of\r\nmigrating DCs is governed by the signal-to-noise
ratio of CCL21 binding to its\r\nreceptor CCR7. Moreover, the haptotactic CCL21
gradient formed in vivo\r\nprovides an optimal shape for DCs to recognize haptotactic
guidance cue.\r\nBy reconstitution of the CCL21 gradient in vitro we were also
able to\r\nstudy the influence of CCR7 signal termination on DC haptotaxis. To
this end,\r\nwe used DCs lacking the G-protein coupled receptor kinase GRK6, which
is\r\nresponsible for CCL21 induced CCR7 receptor phosphorylation and\r\ndesensitization
(Zidar et al., 2009). We found that CCR7 desensitization by\r\nGRK6 is crucial
for maintenance of haptotactic CCL21 gradient sensing in vitro\r\nand confirm
those observations in vivo.\r\nIn the context of the organism, immobilized haptotactic
guidance cues\r\noften coincide and compete with soluble chemotactic guidance
cues. During\r\nwound healing, fibroblasts are exposed and influenced by adhesive
cues and\r\nsoluble factors at the same time (Wu et al., 2012; Wynn, 2008). Similarly,\r\nmigrating
DCs are exposed to both, soluble chemokines (CCL19 and truncated\r\nCCL21) inducing
chemotactic behavior as well as the immobilized CCL21. To\r\nquantitatively assess
these complex coinciding immobilized and soluble\r\nguidance cues, we implemented
our chemokine photo-patterning technique in a\r\nmicrofluidic system allowing
for chemotactic gradient generation. To validate\r\nthe assay, we observed DC
migration in competing CCL19/CCL21\r\nenvironments.\r\nAdhesiveness guided haptotaxis
has been studied intensively over the\r\nlast century. However, quantitative studies
leading to conceptual models are\r\nlargely missing, again due to the lack of
a precisely controllable in vitro assay. A\r\nrequirement for such an in vitro
assay is that it must prevent any uncontrolled\r\ncell adhesion. This can be accomplished
by stable passivation of the surface. In\r\naddition, controlled adhesion must
be sustainable, quantifiable and dose\r\ndependent in order to create homogenous
gradients. Therefore, we developed a novel covalent photo-patterning technique
satisfying all these needs. In\r\ncombination with a sustainable poly-vinyl alcohol
(PVA) surface coating we\r\nwere able to generate gradients of adhesive cue to
direct cell migration. This\r\napproach allowed us to characterize the haptotactic
migratory behavior of\r\nzebrafish keratocytes in vitro. Furthermore, defined
patterns of adhesive cue\r\nallowed us to control for cell shape and growth on
a subcellular scale."
acknowledged_ssus:
- _id: Bio
- _id: PreCl
- _id: LifeSc
acknowledgement: "First, I would like to thank Michael Sixt for being a great supervisor,
mentor and\r\nscientist. I highly appreciate his guidance and continued support.
Furthermore, I\r\nam very grateful that he gave me the exceptional opportunity to
pursue many\r\nideas of which some managed to be included in this thesis.\r\nI owe
sincere thanks to the members of my PhD thesis committee, Daria\r\nSiekhaus, Daniel
Legler and Harald Janovjak. Especially I would like to thank\r\nDaria for her advice
and encouragement during our regular progress meetings.\r\nI also want to thank
the team and fellows of the Boehringer Ingelheim Fond\r\n(BIF) PhD Fellowship for
amazing and inspiring meetings and the BIF for\r\nfinancial support.\r\nImportant
factors for the success of this thesis were the warm, creative\r\nand helpful atmosphere
as well as the team spirit of the whole Sixt Lab.\r\nTherefore I would like to thank
my current and former colleagues Frank Assen,\r\nMarkus Brown, Ingrid de Vries,
Michelle Duggan, Alexander Eichner, Miroslav\r\nHons, Eva Kiermaier, Aglaja Kopf,
Alexander Leithner, Christine Moussion, Jan\r\nMüller, Maria Nemethova, Jörg Renkawitz,
Anne Reversat, Kari Vaahtomeri,\r\nMichele Weber and Stefan Wieser. We had an amazing
time with many\r\nlegendary evenings and events. Along these lines I want to thank
the in vitro\r\ncrew of the lab, Jörg, Anne and Alex, for lots of ideas and productive\r\ndiscussions.
I am sure, some day we will reveal the secret of the ‘splodge’.\r\nI want to thank
the members of the Heisenberg Lab for a great time and\r\nthrilling kicker matches.
In this regard I especially want to thank Maurizio\r\n‘Gnocci’ Monti, Gabriel Krens,
Alex Eichner, Martin Behrndt, Vanessa Barone,Philipp Schmalhorst, Michael Smutny,
Daniel Capek, Anne Reversat, Eva\r\nKiermaier, Frank Assen and Jan Müller for wonderful
after-lunch matches.\r\nI would not have been able to analyze the thousands of cell
trajectories\r\nand probably hundreds of thousands of mouse clicks without the productive\r\ncollaboration
with Veronika Bierbaum and Tobias Bollenbach. Thanks Vroni for\r\ncountless meetings,
discussions and graphs and of course for proofreading and\r\nadvice for this thesis.
For proofreading I also want to thank Evi, Jörg, Jack and\r\nAnne.\r\nI would like
to acknowledge Matthias Mehling for a very productive\r\ncollaboration and for introducing
me into the wild world of microfluidics. Jack\r\nMerrin, for countless wafers, PDMS
coated coverslips and help with anything\r\nmicro-fabrication related. And Maria
Nemethova for establishing the ‘click’\r\npatterning approach with me. Without her
it still would be just one of the ideas…\r\nMany thanks to Ekaterina Papusheva,
Robert Hauschild, Doreen Milius\r\nand Nasser Darwish from the Bioimaging Facility
as well as the Preclinical and\r\nthe Life Science facilities of IST Austria for
excellent technical support. At this\r\npoint I especially want to thank Robert
for countless image analyses and\r\ntechnical ideas. Always interested and creative
he played an essential role in all\r\nof my projects.\r\nAdditionally I want to
thank Ingrid and Gabby for welcoming me warmly\r\nwhen I first started at IST, for
scientific and especially mental support in all\r\nthose years, countless coffee
sessions and Heurigen evenings. #BioimagingFacility #LifeScienceFacility #PreClinicalFacility"
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Jan
full_name: Schwarz, Jan
id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
last_name: Schwarz
citation:
ama: Schwarz J. Quantitative analysis of haptotactic cell migration. 2016.
apa: Schwarz, J. (2016). Quantitative analysis of haptotactic cell migration.
Institute of Science and Technology Austria.
chicago: Schwarz, Jan. “Quantitative Analysis of Haptotactic Cell Migration.” Institute
of Science and Technology Austria, 2016.
ieee: J. Schwarz, “Quantitative analysis of haptotactic cell migration,” Institute
of Science and Technology Austria, 2016.
ista: Schwarz J. 2016. Quantitative analysis of haptotactic cell migration. Institute
of Science and Technology Austria.
mla: Schwarz, Jan. Quantitative Analysis of Haptotactic Cell Migration. Institute
of Science and Technology Austria, 2016.
short: J. Schwarz, Quantitative Analysis of Haptotactic Cell Migration, Institute
of Science and Technology Austria, 2016.
date_created: 2018-12-11T11:50:18Z
date_published: 2016-07-01T00:00:00Z
date_updated: 2023-09-07T11:54:33Z
day: '01'
ddc:
- '570'
degree_awarded: PhD
department:
- _id: MiSi
file:
- access_level: closed
checksum: e3cd6b28f9c5cccb8891855565a2dade
content_type: application/pdf
creator: dernst
date_created: 2019-08-13T10:55:35Z
date_updated: 2019-08-13T10:55:35Z
file_id: '6813'
file_name: Thesis_JSchwarz_final.pdf
file_size: 32044069
relation: main_file
- access_level: open_access
checksum: c3dbe219acf87eed2f46d21d5cca00de
content_type: application/pdf
creator: dernst
date_created: 2021-02-22T11:43:14Z
date_updated: 2021-02-22T11:43:14Z
file_id: '9181'
file_name: 2016_Thesis_JSchwarz.pdf
file_size: 8396717
relation: main_file
success: 1
file_date_updated: 2021-02-22T11:43:14Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '178'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '6231'
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: Quantitative analysis of haptotactic cell migration
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2016'
...