Description du projet
La dynamique de co-développement et d’adaptation de cellules et de matrices extracellulaires
Les cellules à l’intérieur d’un organisme ont une interaction hautement dynamique avec la matrice extracellulaire. Elle est importante non seulement lors de la formation des tissus, mais également impliquée dans le développement de différentes maladies, dont la cardiomyopathie et le cancer. Cette interaction dynamique représente un défi sans précédent en santé, notamment en médecine régénérative. Le projet CoEvolve vise à découvrir les principes biophysiques fondamentaux derrière la dynamique de la matrice extracellulaire de la cellule pour déchiffrer la mécanoadaptation. La recherche impliquera une technologie de manipulation in vitro de pointe pour des études indépendantes et interactives des cellules et de la matrice afin d’étudier comment les cellules perçoivent l’environnement, comment le remodelage matriciel affecte les propriétés mécaniques et comment toutes ces interactions se traduisent par la formation de tissus. Les résultats sont importants pour orienter et faciliter les recherches futures en médecine régénérative et en reconstruction tissulaire.
Objectif
Cells in our body are exceptionally robust: they constantly adapt their properties and behavior to their physical environment. Less appreciated but equally important, the extracellular matrix (ECM) around the cells also adapts to accommodate cell activity. This highly dynamic feedback between the cell and the ECM has been increasingly recognized to play a key role in not only tissue morphogenesis and functions, but also a variety of diseases, from cardiomyopathies to cancer. Moreover, it presents an unprecedented challenge in healthcare and therapeutics, especially regenerative medicine, as progress in this field requires a paradigm shift from conventional, static cell descriptions to a co-evolving cell and tissue physiology. This proposal aims to instigate this transformation by unravelling the fundamental biophysical principles behind cell–matrix dynamic reciprocity and generating a multiscale roadmap of mechanoadaptation critical in functional tissue regeneration.
To achieve this goal, we will develop cutting-edge in vitro manipulation tools to deconstruct and rebuild the dynamics of cells and the ECM independently and interactively, thereby granting us full spatiotemporal control of each component in the system. Using this unique tissue-environment-inspired bottom-up approach, we will dissect how 1) physical changes in the environment are sensed and elicit response by the cell, 2) cell-induced ECM remodeling contributes to mechanical signal transmission, and 3) these local changes are orchestrated into global coordinated mechanoadaptation at the tissue level. The findings will have a broad impact on our fundamental understanding of cell and tissue physiology by identifying novel concepts in mechanoadaptation and will offer specific biomaterial design principles for tissue regeneration. The developed methodology will also advance the field in new directions by enabling further studies on downstream cell and tissue (mal)functions under dynamic conditions.
Champ scientifique
Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
5612 AE Eindhoven
Pays-Bas