Descripción del proyecto
Dinámica de la matriz extracelular y la célula en el codesarrollo y la adaptación
Las células en el interior de organismos presentan una interacción muy dinámica con la matriz extracelular. Esta es importante no solo durante la formación tisular, sino que también interviene en el desarrollo de distintas enfermedades, como la miocardiopatía y el cáncer. Esta interacción dinámica representa un desafío sin precedentes para la atención sanitaria, especialmente la medicina regenerativa. CoEvolve tiene como objetivo desvelar los principios biofísicos fundamentales que sustentan la dinámica matriz extracelular-célula para descifrar la mecanoadaptación. La investigación implicará el uso de una tecnología punta de manipulación «in vitro» para estudios independientes e interactivos de las células y la matriz con el fin de examinar cómo las células perciben el entorno, cómo la remodelación de la matriz afecta a las propiedades mecánicas y cómo estas interacciones se traducen en la formación de tejidos. Los resultados son importantes para dirigir y facilitar futuras investigaciones en medicina regenerativa y reconstrucción tisular.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
5612 AE Eindhoven
Países Bajos