---
_id: '14277'
abstract:
- lang: eng
text: Living tissues are characterized by an intrinsically mechanochemical interplay
of active physical forces and complex biochemical signaling pathways. Either feature
alone can give rise to complex emergent phenomena, for example, mechanically driven
glassy dynamics and rigidity transitions, or chemically driven reaction-diffusion
instabilities. An important question is how to quantitatively assess the contribution
of these different cues to the large-scale dynamics of biological materials. We
address this in Madin-Darby canine kidney (MDCK) monolayers, considering both
mechanochemical feedback between extracellular signal-regulated kinase (ERK) signaling
activity and cellular density as well as a mechanically active tissue rheology
via a self-propelled vertex model. We show that the relative strength of active
migration forces to mechanochemical couplings controls a transition from a uniform
active glass to periodic spatiotemporal waves. We parametrize the model from published
experimental data sets on MDCK monolayers and use it to make new predictions on
the correlation functions of cellular dynamics and the dynamics of topological
defects associated with the oscillatory phase of cells. Interestingly, MDCK monolayers
are best described by an intermediary parameter region in which both mechanochemical
couplings and noisy active propulsion have a strong influence on the dynamics.
Finally, we study how tissue rheology and ERK waves produce feedback on one another
and uncover a mechanism via which tissue fluidity can be controlled by mechanochemical
waves at both the local and global levels.
acknowledgement: We thank all members of the Hannezo group for discussions and suggestions,
as well as Sound Wai Phow for technical assistance. This work received funding from
the European Research Council under the EU Horizon 2020 research and innovation
program Grant Agreement No. 851288 (E.H.), JSPS KAKENHI Grant No. 21H05290, and
the Ministry of Education under the Research Centres of Excellence program through
the MBI at NUS.
article_number: '013001'
article_processing_charge: Yes
article_type: original
author:
- first_name: Daniel R
full_name: Boocock, Daniel R
id: 453AF628-F248-11E8-B48F-1D18A9856A87
last_name: Boocock
orcid: 0000-0002-1585-2631
- first_name: Tsuyoshi
full_name: Hirashima, Tsuyoshi
last_name: Hirashima
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Boocock DR, Hirashima T, Hannezo EB. Interplay between mechanochemical patterning
and glassy dynamics in cellular monolayers. PRX Life. 2023;1(1). doi:10.1103/prxlife.1.013001
apa: Boocock, D. R., Hirashima, T., & Hannezo, E. B. (2023). Interplay between
mechanochemical patterning and glassy dynamics in cellular monolayers. PRX
Life. American Physical Society. https://doi.org/10.1103/prxlife.1.013001
chicago: Boocock, Daniel R, Tsuyoshi Hirashima, and Edouard B Hannezo. “Interplay
between Mechanochemical Patterning and Glassy Dynamics in Cellular Monolayers.”
PRX Life. American Physical Society, 2023. https://doi.org/10.1103/prxlife.1.013001.
ieee: D. R. Boocock, T. Hirashima, and E. B. Hannezo, “Interplay between mechanochemical
patterning and glassy dynamics in cellular monolayers,” PRX Life, vol.
1, no. 1. American Physical Society, 2023.
ista: Boocock DR, Hirashima T, Hannezo EB. 2023. Interplay between mechanochemical
patterning and glassy dynamics in cellular monolayers. PRX Life. 1(1), 013001.
mla: Boocock, Daniel R., et al. “Interplay between Mechanochemical Patterning and
Glassy Dynamics in Cellular Monolayers.” PRX Life, vol. 1, no. 1, 013001,
American Physical Society, 2023, doi:10.1103/prxlife.1.013001.
short: D.R. Boocock, T. Hirashima, E.B. Hannezo, PRX Life 1 (2023).
date_created: 2023-09-06T08:30:59Z
date_published: 2023-07-20T00:00:00Z
date_updated: 2023-09-15T06:39:17Z
day: '20'
ddc:
- '570'
department:
- _id: EdHa
doi: 10.1103/prxlife.1.013001
ec_funded: 1
file:
- access_level: open_access
checksum: f881d98c89eb9f1aa136d7b781511553
content_type: application/pdf
creator: dernst
date_created: 2023-09-15T06:30:50Z
date_updated: 2023-09-15T06:30:50Z
file_id: '14335'
file_name: 2023_PRXLife_Boocock.pdf
file_size: 2559520
relation: main_file
success: 1
file_date_updated: 2023-09-15T06:30:50Z
has_accepted_license: '1'
intvolume: ' 1'
issue: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
project:
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
publication: PRX Life
publication_identifier:
issn:
- 2835-8279
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
status: public
title: Interplay between mechanochemical patterning and glassy dynamics in cellular
monolayers
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: 1
year: '2023'
...
---
_id: '12964'
abstract:
- lang: eng
text: "Pattern formation is of great importance for its contribution across different
biological behaviours. During developmental processes for example, patterns of
chemical gradients are\r\nestablished to determine cell fate and complex tissue
patterns emerge to define structures such\r\nas limbs and vascular networks. Patterns
are also seen in collectively migrating groups, for\r\ninstance traveling waves
of density emerging in moving animal flocks as well as collectively migrating
cells and tissues. To what extent these biological patterns arise spontaneously
through\r\nthe local interaction of individual constituents or are dictated by
higher level instructions is\r\nstill an open question however there is evidence
for the involvement of both types of process.\r\nWhere patterns arise spontaneously
there is a long standing interest in how far the interplay\r\nof mechanics, e.g.
force generation and deformation, and chemistry, e.g. gene regulation\r\nand signaling,
contributes to the behaviour. This is because many systems are able to both\r\nchemically
regulate mechanical force production and chemically sense mechanical deformation,\r\nforming
mechano-chemical feedback loops which can potentially become unstable towards\r\nspatio
and/or temporal patterning.\r\nWe work with experimental collaborators to investigate
the possibility that this type of\r\ninteraction drives pattern formation in biological
systems at different scales. We focus first on\r\ntissue-level ERK-density waves
observed during the wound healing response across different\r\nsystems where many
previous studies have proposed that patterns depend on polarized cell\r\nmigration
and arise from a mechanical flocking-like mechanism. By combining theory with\r\nmechanical
and optogenetic perturbation experiments on in vitro monolayers we instead find\r\nevidence
for mechanochemical pattern formation involving only scalar bilateral feedbacks\r\nbetween
ERK signaling and cell contraction. We perform further modeling and experiment\r\nto
study how this instability couples with polar cell migration in order to produce
a robust\r\nand efficient wound healing response. In a following chapter we implement
ERK-density\r\ncoupling and cell migration in a 2D active vertex model to investigate
the interaction of\r\nERK-density patterning with different tissue rheologies
and find that the spatio-temporal\r\ndynamics are able to both locally and globally
fluidize a tissue across the solid-fluid glass\r\ntransition. In a last chapter
we move towards lower spatial scales in the context of subcellular\r\npatterning
of the cell cytoskeleton where we investigate the transition between phases of\r\nspatially
homogeneous temporal oscillations and chaotic spatio-temporal patterning in the\r\ndynamics
of myosin and ROCK activities (a motor component of the actomyosin cytoskeleton\r\nand
its activator). Experimental evidence supports an intrinsic chemical oscillator
which we\r\nencode in a reaction model and couple to a contractile active gel
description of the cell cortex.\r\nThe model exhibits phases of chemical oscillations
and contractile spatial patterning which\r\nreproduce many features of the dynamics
seen in Drosophila oocyte epithelia in vivo. However,\r\nadditional pharmacological
perturbations to inhibit myosin contractility leaves the role of\r\ncontractile
instability unclear. We discuss alternative hypotheses and investigate the possibility\r\nof
reaction-diffusion instability."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Daniel R
full_name: Boocock, Daniel R
id: 453AF628-F248-11E8-B48F-1D18A9856A87
last_name: Boocock
orcid: 0000-0002-1585-2631
citation:
ama: Boocock DR. Mechanochemical pattern formation across biological scales. 2023.
doi:10.15479/at:ista:12964
apa: Boocock, D. R. (2023). Mechanochemical pattern formation across biological
scales. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12964
chicago: Boocock, Daniel R. “Mechanochemical Pattern Formation across Biological
Scales.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12964.
ieee: D. R. Boocock, “Mechanochemical pattern formation across biological scales,”
Institute of Science and Technology Austria, 2023.
ista: Boocock DR. 2023. Mechanochemical pattern formation across biological scales.
Institute of Science and Technology Austria.
mla: Boocock, Daniel R. Mechanochemical Pattern Formation across Biological Scales.
Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12964.
short: D.R. Boocock, Mechanochemical Pattern Formation across Biological Scales,
Institute of Science and Technology Austria, 2023.
date_created: 2023-05-15T14:52:36Z
date_published: 2023-05-17T00:00:00Z
date_updated: 2023-08-04T11:02:40Z
day: '17'
ddc:
- '530'
degree_awarded: PhD
department:
- _id: GradSch
- _id: EdHa
doi: 10.15479/at:ista:12964
ec_funded: 1
file:
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content_type: application/pdf
creator: dboocock
date_created: 2023-05-17T13:39:54Z
date_updated: 2023-05-19T07:04:25Z
embargo: 2024-05-17
embargo_to: open_access
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file_name: thesis_boocock.pdf
file_size: 40414730
relation: main_file
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content_type: application/zip
creator: dboocock
date_created: 2023-05-17T13:39:53Z
date_updated: 2023-05-17T14:35:13Z
file_id: '12989'
file_name: thesis_boocock.zip
file_size: 34338567
relation: source_file
file_date_updated: 2023-05-19T07:04:25Z
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '05'
oa_version: Published Version
page: '146'
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication_identifier:
isbn:
- 978-3-99078-032-9
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '8602'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
title: Mechanochemical pattern formation across biological scales
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: dissertation
user_id: 8b945eb4-e2f2-11eb-945a-df72226e66a9
year: '2023'
...
---
_id: '8602'
abstract:
- lang: eng
text: Collective cell migration offers a rich field of study for non-equilibrium
physics and cellular biology, revealing phenomena such as glassy dynamics, pattern
formation and active turbulence. However, how mechanical and chemical signalling
are integrated at the cellular level to give rise to such collective behaviours
remains unclear. We address this by focusing on the highly conserved phenomenon
of spatiotemporal waves of density and extracellular signal-regulated kinase (ERK)
activation, which appear both in vitro and in vivo during collective cell migration
and wound healing. First, we propose a biophysical theory, backed by mechanical
and optogenetic perturbation experiments, showing that patterns can be quantitatively
explained by a mechanochemical coupling between active cellular tensions and the
mechanosensitive ERK pathway. Next, we demonstrate how this biophysical mechanism
can robustly induce long-ranged order and migration in a desired orientation,
and we determine the theoretically optimal wavelength and period for inducing
maximal migration towards free edges, which fits well with experimentally observed
dynamics. We thereby provide a bridge between the biophysical origin of spatiotemporal
instabilities and the design principles of robust and efficient long-ranged migration.
acknowledgement: We would like to thank G. Tkacik and all of the members of the Hannezo
and Hirashima groups for useful discussions, X. Trepat for help on traction force
microscopy and M. Matsuda for use of the lab facility. E.H. acknowledges grants
from the Austrian Science Fund (FWF) (P 31639) and the European Research Council
(851288). T.H. acknowledges a grant from JST, PRESTO (JPMJPR1949). This project
has received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant agreement no. 665385 (to D.B.),
from JSPS KAKENHI grant no. 17J02107 (to N.H.) and from the SPIRITS 2018 of Kyoto
University (to E.H. and T.H.).
article_processing_charge: No
article_type: original
author:
- first_name: Daniel R
full_name: Boocock, Daniel R
id: 453AF628-F248-11E8-B48F-1D18A9856A87
last_name: Boocock
orcid: 0000-0002-1585-2631
- first_name: Naoya
full_name: Hino, Naoya
last_name: Hino
- first_name: Natalia
full_name: Ruzickova, Natalia
id: D2761128-D73D-11E9-A1BF-BA0DE6697425
last_name: Ruzickova
- first_name: Tsuyoshi
full_name: Hirashima, Tsuyoshi
last_name: Hirashima
- first_name: Edouard B
full_name: Hannezo, Edouard B
id: 3A9DB764-F248-11E8-B48F-1D18A9856A87
last_name: Hannezo
orcid: 0000-0001-6005-1561
citation:
ama: Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. Theory of mechanochemical
patterning and optimal migration in cell monolayers. Nature Physics. 2021;17:267-274.
doi:10.1038/s41567-020-01037-7
apa: Boocock, D. R., Hino, N., Ruzickova, N., Hirashima, T., & Hannezo, E. B.
(2021). Theory of mechanochemical patterning and optimal migration in cell monolayers.
Nature Physics. Springer Nature. https://doi.org/10.1038/s41567-020-01037-7
chicago: Boocock, Daniel R, Naoya Hino, Natalia Ruzickova, Tsuyoshi Hirashima, and
Edouard B Hannezo. “Theory of Mechanochemical Patterning and Optimal Migration
in Cell Monolayers.” Nature Physics. Springer Nature, 2021. https://doi.org/10.1038/s41567-020-01037-7.
ieee: D. R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, and E. B. Hannezo, “Theory
of mechanochemical patterning and optimal migration in cell monolayers,” Nature
Physics, vol. 17. Springer Nature, pp. 267–274, 2021.
ista: Boocock DR, Hino N, Ruzickova N, Hirashima T, Hannezo EB. 2021. Theory of
mechanochemical patterning and optimal migration in cell monolayers. Nature Physics.
17, 267–274.
mla: Boocock, Daniel R., et al. “Theory of Mechanochemical Patterning and Optimal
Migration in Cell Monolayers.” Nature Physics, vol. 17, Springer Nature,
2021, pp. 267–74, doi:10.1038/s41567-020-01037-7.
short: D.R. Boocock, N. Hino, N. Ruzickova, T. Hirashima, E.B. Hannezo, Nature Physics
17 (2021) 267–274.
date_created: 2020-10-04T22:01:37Z
date_published: 2021-02-01T00:00:00Z
date_updated: 2023-08-04T11:02:41Z
day: '01'
department:
- _id: EdHa
doi: 10.1038/s41567-020-01037-7
ec_funded: 1
external_id:
isi:
- '000573519500002'
intvolume: ' 17'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2020.05.15.096479
month: '02'
oa: 1
oa_version: Preprint
page: 267-274
project:
- _id: 268294B6-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P31639
name: Active mechano-chemical description of the cell cytoskeleton
- _id: 05943252-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '851288'
name: Design Principles of Branching Morphogenesis
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: Nature Physics
publication_identifier:
eissn:
- '17452481'
issn:
- '17452473'
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/wound-healing-waves/
record:
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scopus_import: '1'
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title: Theory of mechanochemical patterning and optimal migration in cell monolayers
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 17
year: '2021'
...