Modelling the mechanical response of living tissues to deformation and fracture

Lead Research Organisation: University College London
Department Name: London Centre for Nanotechnology

Abstract

Epithelial monolayers are one-cell thick tissue sheets that line most of the body surfaces, separating internal and external environments. They are composed of cells whose skeleton is interfaced to one another via specialised adhesive complexes. As part of their function, they must withstand extrinsic mechanical stresses applied at high strain rates. Recently, we have shown that, in response to stretch, epithelial monolayers dissipate stresses on a minute timescale and that relaxation can be described by a power law with an exponential cut-off at timescales larger than ~10 s. This process involves an increase in monolayer length, pointing to active remodelling of cellular biopolymers at the molecular scale during relaxation. Strikingly, monolayers consisting of tens of thousands of cells relax stress with similar dynamics to single rounded cells and both respond similarly to perturbations of the actomyosin cytoskeleton. By contrast, adhesive complexes and intermediate filaments do not relax tissue stress, but form stable connections between cells, allowing monolayers to behave rheologically as single cells. Taken together, these observations imply that the dynamics of the actomyosin cytoskeleton at the molecular-scale controls the rheological properties of epithelial monolayers at the tissue-scale.
Despite these advances, our understanding of how turnover of actomyosin biopolymers at the molecular scale gives rise to complex tissue-scale behaviour remains poor. One strategy to overcome this challenge is to use detailed computational simulations of the molecular processes at play to predict stress response to mechanical deformations. The goal of this PhD project will be to use computational simulations to understand tissue mechanics from the molecular level up. For this, we will adapt the AFFINES simulation environment developed by Dr Banerjee in UCL Physics to include molecular turnover. Next, we will extend the simulation to represent a minimal intercellular junction that will include the cytoskeleton as well as intercellular adhesions. We will implement bond fracture laws to gain an understanding of tissue failure under stress. Indeed, fracture theories developed for inert rigid and ductile materials are not suited to understanding active materials such as living tissues.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/R513143/1 01/10/2018 30/09/2023
2243090 Studentship EP/R513143/1 23/09/2019 30/09/2023 Jack Pache McLarty