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Deconstructing and rebuilding the evolution of cell and tissue mechanoadaptation

Project description

Dynamics of cell and extracellular matrix co-development and adaptation

Cells inside an organism have a highly dynamic interaction with the extracellular matrix. It is important not only during tissue formation but is also implicated in the development of various diseases, including cardiomyopathy and cancer. This dynamic interaction represents an unprecedented challenge in healthcare, especially in regenerative medicine. CoEvolve aims to unravel the fundamental biophysical principles behind cell-extracellular matrix dynamics to decipher mechanoadaptation. Research will involve cutting edge in vitro manipulation technology for independent and interactive studies of cells and the matrix to study how cells sense the environment, how matric remodelling affects mechanical properties, and how all these interactions translate into tissue formation. Outcomes are important for directing and facilitating future research in regenerative medicine and tissue reconstruction.

Objective

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.

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Coordinator

TECHNISCHE UNIVERSITEIT EINDHOVEN
Net EU contribution
€ 1 499 601,00
Address
Groene loper 3
5612 AE Eindhoven
Netherlands

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Region
Zuid-Nederland Noord-Brabant Zuidoost-Noord-Brabant
Activity type
Higher or Secondary Education Establishments
Links
Other funding
€ 0,00

Beneficiaries (1)