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Cell mechanosensing in the extracellular matrix

Project description

Insight into cell mechanosensing

The extracellular matrix (ECM) is a three-dimensional fibrous network of macromolecules that provides a scaffold for cells and maintains the integrity of tissues. The cues generated from probing ECM fibres, known as mechanosensing, help cells adjust their behaviour. However, the ECM has an intricate mechanical response and can undergo irreversible transformations, which can lead to network remodelling. The EU-funded CellMechSensE project aims to establish a theoretical framework to obtain fundamental understanding on how cells behave individually and collectively by mechanically interacting with their surrounding environment. Researchers will use biophysical experiments to develop and calibrate a computational model to simulate and quantitatively assess cell behaviour and further advance knowledge on cell and tissue function.

Objective

Inside tissues, living cells can adhere to a heterogeneous fiber network, the extracellular matrix (ECM). Cells adjust their behavior in response to the local resistance they sense from pulling the neighboring fibers (mechanosensing). As they probe the network and respond to signals, cells can strongly distort the ECM and these deformations can serve as cues for other cells. The cell-generated forces can be large enough to trigger non-linear elastic effects and irreversible transformations of the ECM, resulting in drastic network remodeling. Yet, most theoretical studies have focused on small-force mechanical signals transmitted by an idealized static network. Therefore, the overall research aim of this proposal is to establish a theoretical framework to obtain fundamental understanding on how cells can exploit the non-linearities to extract accurate information by mechanically probing their surroundings. Recent advances in high-resolution, cell-scale imaging and measurement techniques now make it possible to calibrate quantitatively the model from experimental data and high computational power will permit a complete quantitative numerical study of the biological system. This project will bring understanding that will fill a crucial gap of knowledge on the mechanisms controlling individual and collective cell behavior, ultimately allowing key advances on our understanding of body functioning. This comprehension will have a major impact in guiding the design of biological implants and potentially avoid dramatic diseases. With this fellowship, I will extend my research area to biophysics and perform extensive computational simulations under the supervision of Prof. Broedersz. Conducting this research project will raise my academic profile as an expert in mechanical modeling of disordered networks. It will hence increase my chances to achieve my goal of becoming an independent research group leader in statistical modeling of disordered systems in France.

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Topic(s)

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2019

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Coordinator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 174 806,40
Address
GESCHWISTER SCHOLL PLATZ 1
80539 MUNCHEN
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 174 806,40
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