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ForceMorph SIGNED

The integration of cell signalling and mechanical forces in vascular morphology

Total Cost €

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EC-Contrib. €

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Partnership

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Project "ForceMorph" data sheet

The following table provides information about the project.

Coordinator
ABO AKADEMI 

Organization address
address: DOMKYRKOTORGET 3
city: ABO
postcode: 20500
website: http://www.abo.fi

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Finland [FI]
 Total cost 1˙919˙599 €
 EC max contribution 1˙919˙599 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-COG
 Funding Scheme ERC-COG
 Starting year 2018
 Duration (year-month-day) from 2018-03-01   to  2023-02-28

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ABO AKADEMI FI (ABO) coordinator 1˙037˙012.00
2    TECHNISCHE UNIVERSITEIT EINDHOVEN NL (EINDHOVEN) participant 882˙586.00

Map

 Project objective

Cardiovascular diseases represent the principal worldwide medical challenge of the 21st century (WHO), and new concepts to treat, predict and even prevent these diseases are needed. Structural remodelling of the vasculature in response to changes in blood flow is important to maintain mechanical homeostasis, and many diseases are related to defects in tissue morphology and mechanical imbalance. Signalling between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) via the Notch pathway regulates the morphology and structural remodelling of the arterial wall. Importantly, Notch offers handles for therapeutic control and thus opportunities for treatment of malformation and adaptation. However, we lack the essential understanding of how hemodynamic forces integrate with Notch signalling to rationally and responsibly target Notch in vascular therapies. The complexity of the problem requires new tools and an interdisciplinary approach. Our project integrates engineering, computational modelling, with cell biology and in vivo model systems to address the question. In vivo models will validate the in in vitro model systems to ensure that they are reproducible and reflect the reality. Through this integrated approach we will enable new therapeutic developments.

The specific objectives of the project are to:

1) Study EC-VSMC signalling real time, at high resolution by a novel biomimetic 4D Artery-on-Chip that recapitulates the cell-composition, -organisation and hemodynamic forces of the physiological artery

2) Develop a computational model of the arterial wall that include the mechanosensitivity of Notch signalling to predict how the complex interactions affect arterial morphology and remodelling

3) Use in vivo animal models to elucidate how regulation of Notch signalling affects tissue morphology and remodelling in response to changes in hemodynamic conditions

 Deliverables

List of deliverables.
Data management plan Open Research Data Pilot 2019-11-18 10:14:50

Take a look to the deliverables list in detail:  detailed list of ForceMorph deliverables.

 Publications

year authors and title journal last update
List of publications.
2019 Nicole C. A. van Engeland, Freddy Suarez Rodriguez, Adolfo Rivero-Müller, Tommaso Ristori, Camille L. Duran, Oscar M. J. A. Stassen, Daniel Antfolk, Rob C. H. Driessen, Saku Ruohonen, Suvi T. Ruohonen, Salla Nuutinen, Eriika Savontaus, Sandra Loerakker, Kayla J. Bayless, Marika Sjöqvist, Carlijn V. C. Bouten, John E. Eriksson, Cecilia M. Sahlgren
Vimentin regulates Notch signaling strength and arterial remodeling in response to hemodynamic stress
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-019-48218-w
Scientific Reports 9/1 2019-10-14
2018 L. A. Tiemeijer, J-P. Frimat, O. M. J. A. Stassen, C. V. C. Bouten, C. M. Sahlgren
Spatial patterning of the Notch ligand Dll4 controls endothelial sprouting in vitro
published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-018-24646-y
Scientific Reports 8/1 2019-05-08
2018 Sandra Loerakker, Oscar M. J. A. Stassen, Fleur M. ter Huurne, Marcelo Boareto, Carlijn V. C. Bouten, Cecilia M. Sahlgren
Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis
published pages: E3682-E3691, ISSN: 0027-8424, DOI: 10.1073/pnas.1715277115
Proceedings of the National Academy of Sciences 115/16 2019-09-13
2018 Sandra Loerakker, Oscar M. J. A. Stassen, Fleur M. ter Huurne, Marcelo Boareto, Carlijn V. C. Bouten, Cecilia M. Sahlgren
Mechanosensitivity of Jagged–Notch signaling can induce a switch-type behavior in vascular homeostasis
published pages: E3682-E3691, ISSN: 0027-8424, DOI: 10.1073/pnas.1715277115
Proceedings of the National Academy of Sciences 115/16 2019-05-08

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