HEИндивидуална стипендия2025–2027

DISCOVER · Dynamic response of cells to viscoelastic forces

„Хоризонт Европа“ — Действия „Мария Склодовска-Кюри“

Период: 2025-05-01 → 2027-04-30
Финансиране от ЕС: 194 075 €
Участници: 2
Схема: HORIZON-TMA-MSCA-PF-EF

Линиите свързват координатора с партньорите.

Накратко на български

Механобиологията изследва как клетките реагират на физически сили, например при взаимодействие с тъкани, които променят напрежението си във времето. Това помага за създаването на по-точни модели за изучаване на заболявания като рак и фиброза.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Dynamic response of cells to viscoelastic forces

Mechanobiology explores how physical forces affect cellular processes, providing insights into areas like embryogenesis and tumor growth. Cells exert forces onto their environment; the tissue in which they live. These tissues are not purely elastic. In fact, they resist deformation immediately but also relax stress over time, which is influences cell behaviour. And, although this phenomenon called viscoelasticity is increasingly acknowledged, its effects on cell behaviour remain poorly understood. The objective of this project is to uncover mechanisms of the response cells have when interacting with a viscoelastic substrate. For that we envisioned integrating: (i) polyacrylamide substrates with tuneable stiffness and defined relaxation behaviour, (ii) experiments on living cells to quantify and compare dynamic responses across these mechanical conditions, and (iii) computational modelling and inference tools that connect measured dynamics to interpretable mechanistic descriptions of the cells. The research presented addresses a biomedical need: mechanical changes in tissues are a hallmark of major health issues, such as mentioned (cancer, fibrosis etc). By improving how viscoelasticity is engineered, measured and interpreted in cell culture, the project contributes to more physiologically relevant and reproducible mechanobiology assays, supporting better experimental models for studying disease-relevant cell states and therapies.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

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.

Оригинален текст от CORDIS (на английски).

Участници

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA · BarcelonaКоординаторИспания
TECHNISCHE UNIVERSITEIT DELFT · DelftНидерландия