Deconstructing Cell-Extracellular Matrix Co-Adaptive Mechanisms by Hydrogel Mechano-Actuation in Pathological Microenvironments

Fibrosis, characterized by tissue stiffening and altered FAK signaling patterns, is highly prevalent in Europe and places a significant financial burden on our healthcare system. However effective treatments are hampered by the lack of accurate disease models. While most of our disease understanding comes from studying cells under static conditions, in vivo cell interactions are far from static, leading to inconsistencies between lab models, suggesting that tissue stiffness alone drives fibrosis, and clinical observations, indicating otherwise.The ECMAP project aims to bridge this gap in our knowledge by introducing a novel approach that replicates the dynamic processes driving fibrosis. Professor Fernandez's lab has recently discovered a molecular link between mechanical forces and FAK signaling at individual focal adhesions (IFAs), crucial in functional tissue-scale processes. This project will elucidate the role of increased FAK activity at IFAs during force transmission and mechanosensing in fibrosis progression. This will be achieved by combining molecular devices, light-activated ligands, and cutting-edge microscopy tools to monitor (fibrotic and healthy) FAK signaling in real-time while applying controlled forces at IFAs. This innovative platform for studying fibrosis progression at an unprecedented molecular resolution aims to facilitate drug discovery, enhance early diagnosis, and develop new tools for monitoring fibrosis and other tissue mechanics diseases. Our work represents a paradigm shift in treating mechano-diseases, aligning with urgent healthcare needs and offering hope for more targeted and effective solutions.