Descrizione del progetto
Dinamiche di co-sviluppo e adattamento delle cellule e della matrice extracellulare
Le cellule all’interno di un organismo hanno un’interazione altamente dinamica con la matrice extracellulare. È importante non solo durante la formazione dei tessuti, ma anche nello sviluppo di varie malattie, tra cui cardiomiopatie e cancro. Questa interazione dinamica rappresenta una sfida senza precedenti nel settore sanitario, in particolare nella medicina rigenerativa. CoEvolve mira a svelare i principi biofisici fondamentali alla base della dinamica cellula/matrice extracellulare per decifrare l’adattamento meccanico. La ricerca coinvolgerà una tecnologia di manipolazione in vitro all’avanguardia per studi indipendenti e interattivi sulle cellule e sulla matrice per studiare come le cellule percepiscono l’ambiente, come il rimodellamento della matrice influisce sulle proprietà meccaniche e come tutte queste interazioni si traducono in formazione di tessuti. I risultati sono importanti per dirigere e agevolare la ricerca futura nella medicina rigenerativa e nella ricostruzione dei tessuti.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
5612 AE Eindhoven
Paesi Bassi