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Active FELLOWSHIP UKRI Gateway to Research

Rheology and Fracture in Confluent Cell Layers

£1.92M GBP

Funder Horizon Europe Guarantee
Recipient Organization University of Oxford
Country United Kingdom
Start Date Sep 30, 2024
End Date Sep 29, 2026
Duration 729 days
Number of Grantees 1
Roles Principal Investigator
Data Source UKRI Gateway to Research
Grant ID EP/Z002761/1
Grant Description

Epithelial tissues encompass a large range of biological tissues widely present in animals, from the skin to the coating of several organs and blood vessels.

Given this, they also take part in several key processes ranging from tissue development to homeostasis and wound healing.

To properly function, the tissue is required to handle great deals of stress, otherwise it can lead to failure, which is usually accompanied by rupture.

Despite its importance, exceptionally little is known regarding the mechanical limits of tissues when subjected to large deformations.

It has been recently discussed the role of the supracellular keratin filament network in controlling the tissues' strength, suggesting that fracture depends strongly on the cell-cell adhesion mediated by these filaments.

This cemented fracture in epithelial monolayers as a multiscale process which related rupture of bonds at the molecular-scale to cellular forces from tissue-scale deformations, and further called to attention the importance of characterizing tissue rheology.

With my proposal RheoCell, I aim to address this issue by putting forward an interdisciplinary approach which exploits soft matter and mechanobiology to investigate the rheology and fracture of epithelial monolayers through coarse-grained modelling using phase field models.

By combining numerical simulations with experiments, I intend to put forward a mesoscale description of the viscoelastic response of tissues and how collective cell behavior plays a role in tissue response during externally imposed deformations.

I will then leverage these results to propose new theories on tissue failure that are able to relate cell-cell adhesion, compressibility, and active processes to crack initiation and propagation.

My proposal will ultimately help guide the engineering of new artificial tissues and inspire future studies where the response of the tissue to deformations plays a significant role.

All Grantees

University of Oxford

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