---
_id: '674'
abstract:
- lang: eng
  text: Navigation of cells along gradients of guidance cues is a determining step
    in many developmental and immunological processes. Gradients can either be soluble
    or immobilized to tissues as demonstrated for the haptotactic migration of dendritic
    cells (DCs) toward higher concentrations of immobilized chemokine CCL21. To elucidate
    how gradient characteristics govern cellular response patterns, we here introduce
    an in vitro system allowing to track migratory responses of DCs to precisely controlled
    immobilized gradients of CCL21. We find that haptotactic sensing depends on the
    absolute CCL21 concentration and local steepness of the gradient, consistent with
    a scenario where DC directionality is governed by the signal-to-noise ratio of
    CCL21 binding to the receptor CCR7. We find that the conditions for optimal DC
    guidance are perfectly provided by the CCL21 gradients we measure in vivo. Furthermore,
    we find that CCR7 signal termination by the G-protein-coupled receptor kinase
    6 (GRK6) is crucial for haptotactic but dispensable for chemotactic CCL21 gradient
    sensing in vitro and confirm those observations in vivo. These findings suggest
    that stable, tissue-bound CCL21 gradients as sustainable “roads” ensure optimal
    guidance in vivo.
author:
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Veronika
  full_name: Bierbaum, Veronika
  id: 3FD04378-F248-11E8-B48F-1D18A9856A87
  last_name: Bierbaum
- first_name: Kari
  full_name: Vaahtomeri, Kari
  id: 368EE576-F248-11E8-B48F-1D18A9856A87
  last_name: Vaahtomeri
  orcid: 0000-0001-7829-3518
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Markus
  full_name: Brown, Markus
  id: 3DAB9AFC-F248-11E8-B48F-1D18A9856A87
  last_name: Brown
- first_name: Ingrid
  full_name: De Vries, Ingrid
  id: 4C7D837E-F248-11E8-B48F-1D18A9856A87
  last_name: De Vries
- first_name: Alexander F
  full_name: Leithner, Alexander F
  id: 3B1B77E4-F248-11E8-B48F-1D18A9856A87
  last_name: Leithner
- first_name: Anne
  full_name: Reversat, Anne
  id: 35B76592-F248-11E8-B48F-1D18A9856A87
  last_name: Reversat
  orcid: 0000-0003-0666-8928
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Teresa
  full_name: Tarrant, Teresa
  last_name: Tarrant
- first_name: Tobias
  full_name: Bollenbach, Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
- 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, Bierbaum V, Vaahtomeri K, et al. Dendritic cells interpret haptotactic
    chemokine gradients in a manner governed by signal to noise ratio and dependent
    on GRK6. <i>Current Biology</i>. 2017;27(9):1314-1325. doi:<a href="https://doi.org/10.1016/j.cub.2017.04.004">10.1016/j.cub.2017.04.004</a>
  apa: Schwarz, J., Bierbaum, V., Vaahtomeri, K., Hauschild, R., Brown, M., de Vries,
    I., … Sixt, M. K. (2017). Dendritic cells interpret haptotactic chemokine gradients
    in a manner governed by signal to noise ratio and dependent on GRK6. <i>Current
    Biology</i>. Cell Press. <a href="https://doi.org/10.1016/j.cub.2017.04.004">https://doi.org/10.1016/j.cub.2017.04.004</a>
  chicago: Schwarz, Jan, Veronika Bierbaum, Kari Vaahtomeri, Robert Hauschild, Markus
    Brown, Ingrid de Vries, Alexander F Leithner, et al. “Dendritic Cells Interpret
    Haptotactic Chemokine Gradients in a Manner Governed by Signal to Noise Ratio
    and Dependent on GRK6.” <i>Current Biology</i>. Cell Press, 2017. <a href="https://doi.org/10.1016/j.cub.2017.04.004">https://doi.org/10.1016/j.cub.2017.04.004</a>.
  ieee: J. Schwarz <i>et al.</i>, “Dendritic cells interpret haptotactic chemokine
    gradients in a manner governed by signal to noise ratio and dependent on GRK6,”
    <i>Current Biology</i>, vol. 27, no. 9. Cell Press, pp. 1314–1325, 2017.
  ista: Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner
    AF, Reversat A, Merrin J, Tarrant T, Bollenbach MT, Sixt MK. 2017. Dendritic cells
    interpret haptotactic chemokine gradients in a manner governed by signal to noise
    ratio and dependent on GRK6. Current Biology. 27(9), 1314–1325.
  mla: Schwarz, Jan, et al. “Dendritic Cells Interpret Haptotactic Chemokine Gradients
    in a Manner Governed by Signal to Noise Ratio and Dependent on GRK6.” <i>Current
    Biology</i>, vol. 27, no. 9, Cell Press, 2017, pp. 1314–25, doi:<a href="https://doi.org/10.1016/j.cub.2017.04.004">10.1016/j.cub.2017.04.004</a>.
  short: J. Schwarz, V. Bierbaum, K. Vaahtomeri, R. Hauschild, M. Brown, I. de Vries,
    A.F. Leithner, A. Reversat, J. Merrin, T. Tarrant, M.T. Bollenbach, M.K. Sixt,
    Current Biology 27 (2017) 1314–1325.
date_created: 2018-12-11T11:47:51Z
date_published: 2017-05-09T00:00:00Z
date_updated: 2023-02-23T12:50:44Z
day: '09'
department:
- _id: MiSi
- _id: Bio
- _id: NanoFab
doi: 10.1016/j.cub.2017.04.004
ec_funded: 1
intvolume: '        27'
issue: '9'
language:
- iso: eng
month: '05'
oa_version: None
page: 1314 - 1325
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
  call_identifier: FP7
  grant_number: '291734'
  name: International IST Postdoc Fellowship Programme
- _id: 25A8E5EA-B435-11E9-9278-68D0E5697425
  call_identifier: FWF
  grant_number: Y 564-B12
  name: Cytoskeletal force generation and transduction of leukocytes (FWF)
publication: Current Biology
publication_identifier:
  issn:
  - '09609822'
publication_status: published
publisher: Cell Press
publist_id: '7050'
quality_controlled: '1'
scopus_import: 1
status: public
title: Dendritic cells interpret haptotactic chemokine gradients in a manner governed
  by signal to noise ratio and dependent on GRK6
type: journal_article
user_id: 4435EBFC-F248-11E8-B48F-1D18A9856A87
volume: 27
year: '2017'
...
---
_id: '1154'
abstract:
- lang: eng
  text: "Cellular locomotion is a central hallmark of eukaryotic life. It is governed
    by cell-extrinsic molecular factors, which can either emerge in the soluble phase
    or as immobilized, often adhesive ligands. To encode for direction, every cue
    must be present as a spatial or temporal gradient. Here, we developed a microfluidic
    chamber that allows measurement of cell migration in combined response to surface
    immobilized and soluble molecular gradients. As a proof of principle we study
    the response of dendritic cells to their major guidance cues, chemokines. The
    majority of data on chemokine gradient sensing is based on in vitro studies employing
    soluble gradients. Despite evidence suggesting that in vivo chemokines are often
    immobilized to sugar residues, limited information is available how cells respond
    to immobilized chemokines. We tracked migration of dendritic cells towards immobilized
    gradients of the chemokine CCL21 and varying superimposed soluble gradients of
    CCL19. Differential migratory patterns illustrate the potential of our setup to
    quantitatively study the competitive response to both types of gradients. Beyond
    chemokines our approach is broadly applicable to alternative systems of chemo-
    and haptotaxis such as cells migrating along gradients of adhesion receptor ligands
    vs. any soluble cue. \r\n"
acknowledgement: 'This work was supported by the Swiss National Science Foundation
  (Ambizione fellowship; PZ00P3-154733 to M.M.), the Swiss Multiple Sclerosis Society
  (research support to M.M.), a fellowship from the Boehringer Ingelheim Fonds (BIF)
  to J.S., the European Research Council (grant ERC GA 281556) and a START award from
  the Austrian Science Foundation (FWF) to M.S. #BioimagingFacility'
article_number: '36440'
author:
- first_name: Jan
  full_name: Schwarz, Jan
  id: 346C1EC6-F248-11E8-B48F-1D18A9856A87
  last_name: Schwarz
- first_name: Veronika
  full_name: Bierbaum, Veronika
  id: 3FD04378-F248-11E8-B48F-1D18A9856A87
  last_name: Bierbaum
- first_name: Jack
  full_name: Merrin, Jack
  id: 4515C308-F248-11E8-B48F-1D18A9856A87
  last_name: Merrin
  orcid: 0000-0001-5145-4609
- first_name: Tino
  full_name: Frank, Tino
  last_name: Frank
- first_name: Robert
  full_name: Hauschild, Robert
  id: 4E01D6B4-F248-11E8-B48F-1D18A9856A87
  last_name: Hauschild
  orcid: 0000-0001-9843-3522
- first_name: Mark Tobias
  full_name: Bollenbach, Mark Tobias
  id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
  last_name: Bollenbach
  orcid: 0000-0003-4398-476X
- first_name: Savaş
  full_name: Tay, Savaş
  last_name: Tay
- 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: Matthias
  full_name: Mehling, Matthias
  id: 3C23B994-F248-11E8-B48F-1D18A9856A87
  last_name: Mehling
  orcid: 0000-0001-8599-1226
citation:
  ama: Schwarz J, Bierbaum V, Merrin J, et al. A microfluidic device for measuring
    cell migration towards substrate bound and soluble chemokine gradients. <i>Scientific
    Reports</i>. 2016;6. doi:<a href="https://doi.org/10.1038/srep36440">10.1038/srep36440</a>
  apa: Schwarz, J., Bierbaum, V., Merrin, J., Frank, T., Hauschild, R., Bollenbach,
    M. T., … Mehling, M. (2016). A microfluidic device for measuring cell migration
    towards substrate bound and soluble chemokine gradients. <i>Scientific Reports</i>.
    Nature Publishing Group. <a href="https://doi.org/10.1038/srep36440">https://doi.org/10.1038/srep36440</a>
  chicago: Schwarz, Jan, Veronika Bierbaum, Jack Merrin, Tino Frank, Robert Hauschild,
    Mark Tobias Bollenbach, Savaş Tay, Michael K Sixt, and Matthias Mehling. “A Microfluidic
    Device for Measuring Cell Migration towards Substrate Bound and Soluble Chemokine
    Gradients.” <i>Scientific Reports</i>. Nature Publishing Group, 2016. <a href="https://doi.org/10.1038/srep36440">https://doi.org/10.1038/srep36440</a>.
  ieee: J. Schwarz <i>et al.</i>, “A microfluidic device for measuring cell migration
    towards substrate bound and soluble chemokine gradients,” <i>Scientific Reports</i>,
    vol. 6. Nature Publishing Group, 2016.
  ista: Schwarz J, Bierbaum V, Merrin J, Frank T, Hauschild R, Bollenbach MT, Tay
    S, Sixt MK, Mehling M. 2016. A microfluidic device for measuring cell migration
    towards substrate bound and soluble chemokine gradients. Scientific Reports. 6,
    36440.
  mla: Schwarz, Jan, et al. “A Microfluidic Device for Measuring Cell Migration towards
    Substrate Bound and Soluble Chemokine Gradients.” <i>Scientific Reports</i>, vol.
    6, 36440, Nature Publishing Group, 2016, doi:<a href="https://doi.org/10.1038/srep36440">10.1038/srep36440</a>.
  short: J. Schwarz, V. Bierbaum, J. Merrin, T. Frank, R. Hauschild, M.T. Bollenbach,
    S. Tay, M.K. Sixt, M. Mehling, Scientific Reports 6 (2016).
date_created: 2018-12-11T11:50:27Z
date_published: 2016-11-07T00:00:00Z
date_updated: 2021-01-12T06:48:41Z
day: '07'
ddc:
- '579'
department:
- _id: MiSi
- _id: NanoFab
- _id: Bio
- _id: ToBo
doi: 10.1038/srep36440
ec_funded: 1
file:
- access_level: open_access
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:09:32Z
  date_updated: 2018-12-12T10:09:32Z
  file_id: '4756'
  file_name: IST-2017-744-v1+1_srep36440.pdf
  file_size: 2353456
  relation: main_file
file_date_updated: 2018-12-12T10:09:32Z
has_accepted_license: '1'
intvolume: '         6'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
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: Scientific Reports
publication_status: published
publisher: Nature Publishing Group
publist_id: '6204'
pubrep_id: '744'
quality_controlled: '1'
scopus_import: 1
status: public
title: A microfluidic device for measuring cell migration towards substrate bound
  and soluble chemokine gradients
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 6
year: '2016'
...
---
_id: '1530'
abstract:
- lang: eng
  text: In growing cells, protein synthesis and cell growth are typically not synchronous,
    and, thus, protein concentrations vary over the cell division cycle. We have developed
    a theoretical description of genetic regulatory systems in bacteria that explicitly
    considers the cell division cycle to investigate its impact on gene expression.
    We calculate the cell-to-cell variations arising from cells being at different
    stages in the division cycle for unregulated genes and for basic regulatory mechanisms.
    These variations contribute to the extrinsic noise observed in single-cell experiments,
    and are most significant for proteins with short lifetimes. Negative autoregulation
    buffers against variation of protein concentration over the division cycle, but
    the effect is found to be relatively weak. Stronger buffering is achieved by an
    increased protein lifetime. Positive autoregulation can strongly amplify such
    variation if the parameters are set to values that lead to resonance-like behaviour.
    For cooperative positive autoregulation, the concentration variation over the
    division cycle diminishes the parameter region of bistability and modulates the
    switching times between the two stable states. The same effects are seen for a
    two-gene mutual-repression toggle switch. By contrast, an oscillatory circuit,
    the repressilator, is only weakly affected by the division cycle.
article_number: '066003'
author:
- first_name: Veronika
  full_name: Bierbaum, Veronika
  id: 3FD04378-F248-11E8-B48F-1D18A9856A87
  last_name: Bierbaum
- first_name: Stefan
  full_name: Klumpp, Stefan
  last_name: Klumpp
citation:
  ama: Bierbaum V, Klumpp S. Impact of the cell division cycle on gene circuits. <i>Physical
    Biology</i>. 2015;12(6). doi:<a href="https://doi.org/10.1088/1478-3975/12/6/066003">10.1088/1478-3975/12/6/066003</a>
  apa: Bierbaum, V., &#38; Klumpp, S. (2015). Impact of the cell division cycle on
    gene circuits. <i>Physical Biology</i>. IOP Publishing Ltd. <a href="https://doi.org/10.1088/1478-3975/12/6/066003">https://doi.org/10.1088/1478-3975/12/6/066003</a>
  chicago: Bierbaum, Veronika, and Stefan Klumpp. “Impact of the Cell Division Cycle
    on Gene Circuits.” <i>Physical Biology</i>. IOP Publishing Ltd., 2015. <a href="https://doi.org/10.1088/1478-3975/12/6/066003">https://doi.org/10.1088/1478-3975/12/6/066003</a>.
  ieee: V. Bierbaum and S. Klumpp, “Impact of the cell division cycle on gene circuits,”
    <i>Physical Biology</i>, vol. 12, no. 6. IOP Publishing Ltd., 2015.
  ista: Bierbaum V, Klumpp S. 2015. Impact of the cell division cycle on gene circuits.
    Physical Biology. 12(6), 066003.
  mla: Bierbaum, Veronika, and Stefan Klumpp. “Impact of the Cell Division Cycle on
    Gene Circuits.” <i>Physical Biology</i>, vol. 12, no. 6, 066003, IOP Publishing
    Ltd., 2015, doi:<a href="https://doi.org/10.1088/1478-3975/12/6/066003">10.1088/1478-3975/12/6/066003</a>.
  short: V. Bierbaum, S. Klumpp, Physical Biology 12 (2015).
date_created: 2018-12-11T11:52:33Z
date_published: 2015-09-25T00:00:00Z
date_updated: 2021-01-12T06:51:25Z
day: '25'
department:
- _id: MiSi
doi: 10.1088/1478-3975/12/6/066003
intvolume: '        12'
issue: '6'
language:
- iso: eng
month: '09'
oa_version: None
publication: Physical Biology
publication_status: published
publisher: IOP Publishing Ltd.
publist_id: '5641'
quality_controlled: '1'
scopus_import: 1
status: public
title: Impact of the cell division cycle on gene circuits
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2015'
...