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Deconstructing and rebuilding the evolution of cell and tissue mechanoadaptation

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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Host institution

TECHNISCHE UNIVERSITEIT EINDHOVEN

Address

Groene Loper 3
5612 Ae Eindhoven

Netherlands

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 499 601

Beneficiaries (1)

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TECHNISCHE UNIVERSITEIT EINDHOVEN

Netherlands

EU Contribution

€ 1 499 601

Project information

Grant agreement ID: 851960

Status

Grant agreement signed

  • Start date

    1 January 2020

  • End date

    31 December 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 499 601

  • EU contribution

    € 1 499 601

Hosted by:

TECHNISCHE UNIVERSITEIT EINDHOVEN

Netherlands