Dynamic response of cells to viscoelastic forces

Project Information

DISCOVER

Grant agreement ID: 101206469

DOI

10.3030/101206469

Project terminated on 15 December 2025

EC signature date 10 April 2025

Start date 1 May 2025

End date 30 April 2027

Funded under

• Marie Skłodowska-Curie Actions (MSCA)

Total cost

No data

EU contribution

€ 194 074,56

Coordinated by

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Spain

Periodic Reporting for period 1 - DISCOVER (Dynamic response of cells to viscoelastic forces)

Reporting period: 2025-05-01 to 2027-04-30

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Within the shortened project duration (months 1–7.5) the work performed focused on building the experimental and computational basis needed to study cell responses to viscoelasticity.

First, we established a reproducible way to produce viscoelastic hydrogels for cell culture and created a small, well-defined set of substrate conditions spanning soft and stiffer mechanics with different stress-relaxation behaviour. The mechanical characterisation, mainly done via Nanoindentation, showed an important practical limitation of the chosen polyacrylamide material system: the time-dependent relaxation behaviour is significantly influenced by fluid flow within the material (poroelastic effects). This matters because it constrains how independently and how strongly certain relaxation timescales can be tuned. To broaden the material platform, a parallel collaboration advanced a DNA-based hydrogel microparticle approach that offers a more programmable route to tune mechanical behaviour. The final integration into a DNA-Polyacrylamide-gel is pending.

In parallel, a computational model for the cellular response to viscoelastic substrates was developed. Based on the data (predictions) generated by this model, a computational “inference” component was developed: an equation-discovery pipeline was implemented, specific to mathematical problems as posed by this specific biological problem. This tool is designed to help extract compact, interpretable models and to connect experimental observations back to mechanistic descriptions of force transmission.

Finally, biological feasibility was established by demonstrating robust cell adhesion and spreading on the engineered substrates, and by initiating fast imaging approaches needed to access the timescales relevant for dynamic force transmission.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Within the shortened project duration (months 1–7.5) the project delivered a set of highly reproducible viscoelastic hydrogels. A key insight was that, in the chosen polyacrylamide system, time-dependent relaxation is strongly influenced by poroelastic effects, which limits how independently and how strongly relaxation timescales can be tuned. To address this limitation and broaden the overall material platform, the project contributed to a collaboration on DNA-based hydrogel microparticles, which led to a submitted manuscript. In parallel, the project produced a computational modelling and equation-discovery pipeline tailored to the dynamical structure of cellular force transmission on viscoelastic substrates. The inference workflow is publicly available online and provides a bridge between mechanistic clutch-type models and data-driven discovery.