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Dynamic response of cells to viscoelastic forces

Project description

Insight into tissue material properties

Mechanical forces shape cellular behaviour, especially during embryonic development and cancer. While most research has examined elastic materials, biological tissues are viscoelastic, meaning they exhibit both fluid-like and solid-like properties. However, it is poorly understood how viscoelasticity influences cell behaviour. With the support of the Marie Skłodowska-Curie Actions programme, the DISCOVER project will engineer hydrogels with tunable viscoelasticity to study fibroblast responses using advanced live cell imaging. Coupled with computational modelling, the work will reveal how force-sensitive proteins and cytoskeletal dynamics integrate complex mechanical cues. The generated knowledge will have broad implications for cancer research, organoid biology and regenerative medicine.

Objective

Mechanobiology explores how physical forces affect cellular processes, providing insights into areas like embryogenesis and tumor growth. While most studies focus on cells responding to forces stemming from elastic materials, biological materials are viscoelastic. Single materials elastically resist deformation while viscously relaxing with a multitude of relaxation times. Whereas viscoelasticity is increasingly acknowledged in mechanobiology research, its effects on cell behaviour remain poorly understood. This project aims to uncover the mechanisms behind viscoelastic mechanotransduction, by considering cell dynamics and multiple relaxation times within the cell environment. I will engineer hydrogels with tuneable viscoelastic properties, culture fibroblasts on them and employ cutting-edge (live cell) fluorescence microscopy and computational modeling of the cellular mechanotransduction. The hydrogels' elasticity will be tuned by the 3D crosslinked network, and viscosity by linear polymers within the network. Considering properties of gel and force-sensitive proteins inside the cell a stochastic simulation will predict and explain cell behavior, a data-driven model will infer properties from experimentally observed cell behavior. Experimentally, I will characterize mouse fibroblast mechanotransduction on these gels, focusing on adhesion, cytoskeleton, and YAP/TAZ activity, using fluorescent proteins and confocal microscopy. Chemical perturbations of the cytoskeleton will validate the model. Spanning experimental and theoretical methods from material science, cell biology, and computational sciences, this project will shed light on a crucial but underexplored aspect of mechanobiology. As mechanical changes in the cell enviroment are a hallmark of many tumors, this research is particularly relevant for oncology. Further, the models and insights gained will have an impact on the study of organoids in viscoelastic 3D matrices, as well as fibrosis and would healing.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
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.

€ 194 074,56
Address
CARRER BALDIRI REIXAC PLANTA 2A 10-12
08028 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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