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Details of Grant 

EPSRC Reference: EP/M012964/1
Title: Modelling the mechanics of epithelial sheets on soft substrates: nonlinearity, feedback and dissipation
Principal Investigator: Dunlop, Dr C
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Mathematics
Organisation: University of Surrey
Scheme: First Grant - Revised 2009
Starts: 17 March 2015 Ends: 16 October 2017 Value (£): 95,703
EPSRC Research Topic Classifications:
Biomechanics & Rehabilitation Tissue Engineering
EPSRC Industrial Sector Classifications:
Related Grants:
Panel History:
Panel DatePanel NameOutcome
08 Oct 2014 Engineering Prioritisation Panel Meeting 8th October 2014 Announced
Summary on Grant Application Form
The rapid expansion of experimental biophysics is driving a new realisation of the fundamental importance of mechanical forces in biology. Cells are now seen to be exquisitely sensitive to their mechanical microenvironments, exhibiting very different behaviours when exposed to e.g. soft or stiff gels. Particularly striking is work showing that stem cells can turn into very different cell types ranging from brain, bone to muscle depending on the stiffness of the gel they are grown on. As a result of such studies it has become clear that successful tissue engineering is dependent on making tissue scaffolds that are finely tuned not just in their biochemical, but also in their mechanical properties.

A primary mechanism by which cells sense the mechanical properties of their environments is by exploiting the contractility of their internal cytoskeletal networks to 'pull' on the external gel. For single cells, the strength of this pulling force is traditionally measured using Traction Force Microscopy (TFM). In TFM the amount that a cell displaces the gel is carefully measured and correlated to the mechanical activity of the individual cell. However in tissues, obtaining and interpreting such experimental data is significantly complicated and instead the magnitudes of cellular forces are usually inferred through indirect methods such as by mechanical relaxation after laser cutting.

We propose here a different approach using mathematical abstraction to couple descriptions of active cellular behaviours into classical elasticity models. The result will be an innovative suite of continuum models that integrate cell contractility, cell mechanotransduction, stress relaxation and the complex material properties of the underlying gel matrix into a complete model of tissue-gel interaction. This work can be used to interpret experimental data and predict cellular response to changes in the mechanical properties of the surrounding environment. The models developed will also inform future biomechanical modelling work as applied to tissue development and morphogenesis.

The modelling work is split into various steps that build up the complete picture that we are aiming for. The modules are: A) A model for the bonding of a contractile epithelial tissue to an underlying gel incorporating stress relaxation; B) Incorporating feedback control of cellular behaviour into the system; and C) A consideration of the physical complexities of the gel underlying the tissue layer.

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