Models for cellular force generation and the cell-substrate interface
Lead Research Organisation:
University of Surrey
Department Name: Mathematics
Abstract
Cells are able to interact with their environments through a variety of chemical and physical signalling mechanisms, with it becoming increasingly clear that physical force plays a crucial role in determining cellular behaviour and coordination. It is clear that cells respond very differently depending on the mechanical properties of their environments; understanding these differences in their behaviour is crucial for tissue engineering applications and to understand how the mechanical microenvironment may affect, for example, cancer growth and invasion.
This project focuses on developing advanced mathematical models to describe the physical forces exerted by a single cell or cell layer when adhered to a gel layer and to elucidate the complex interplay between cellular dynamics and the mechanical microenvironment. The model context focuses on the most common biophysical experimental set-ups for investigating cellular forces. These experiments generally work from inferring cellular forces from measurements of the observed substrate deformation, using experimentally determined knowledge of the mechanical response of the designed substrates. The underlying substrates range from elastic gels (as for Traction Force Microscopy studies) to arrays of micropillars.
The modelling framework being developed is based in continuum elasticity theory additionally using active matter theory to describe cellular contractility, which is the primary mechanism of force generation. On the time scale of experimental observations the cell or cell layer is assumed to be in mechanical equilibrium. This project is developing detailed mathematical descriptions of the cell-gel interface and also of the mechanisms of force generation. A key objective is to explain the observed cellular adaptations to changes in the mechanical properties of the underlying gel. The models are being analysed and solved using both analytical approaches (exploiting approximations and symmetry arguments) and using Finite Element Methods.
This project focuses on developing advanced mathematical models to describe the physical forces exerted by a single cell or cell layer when adhered to a gel layer and to elucidate the complex interplay between cellular dynamics and the mechanical microenvironment. The model context focuses on the most common biophysical experimental set-ups for investigating cellular forces. These experiments generally work from inferring cellular forces from measurements of the observed substrate deformation, using experimentally determined knowledge of the mechanical response of the designed substrates. The underlying substrates range from elastic gels (as for Traction Force Microscopy studies) to arrays of micropillars.
The modelling framework being developed is based in continuum elasticity theory additionally using active matter theory to describe cellular contractility, which is the primary mechanism of force generation. On the time scale of experimental observations the cell or cell layer is assumed to be in mechanical equilibrium. This project is developing detailed mathematical descriptions of the cell-gel interface and also of the mechanisms of force generation. A key objective is to explain the observed cellular adaptations to changes in the mechanical properties of the underlying gel. The models are being analysed and solved using both analytical approaches (exploiting approximations and symmetry arguments) and using Finite Element Methods.
Organisations
Studentship Projects
Project Reference | Relationship | Related To | Start | End | Student Name |
---|---|---|---|---|---|
EP/N509772/1 | 01/10/2016 | 30/09/2021 | |||
1944689 | Studentship | EP/N509772/1 | 01/10/2017 | 31/03/2021 | Josephine Solowiej-Wedderburn |
Description | 6 month funding extension to: Models for cellular force generation and the cell-substrate interface |
Amount | £10,000 (GBP) |
Funding ID | 1944689 |
Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
Sector | Public |
Country | United Kingdom |
Start | 10/2020 |
End | 03/2021 |
Description | BAMC 2021 (Glasgow) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | Gave a talk at the BAMC virtual conference, engaging with fellow research users (approximately 40 attended on zoom). |
Year(s) Of Engagement Activity | 2021 |
URL | https://sites.google.com/view/bmcbamc2021/home |
Description | Cell la Vie conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Presented a poster at a virtual conference held between the French Society for Cell Biology and British Society for Cell Biology. This allowed me to share my theoretical work with experimentalists. We have since been in contact with an experimentalist also presenting at the conference and have the potential to collaborate. |
Year(s) Of Engagement Activity | 2021 |
URL | https://sbcf.fr/en/event/cell-la-vie-2021-online/ |
Description | STEM for Britain |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | I was 1 of 30 researchers selected to produce a poster for the mathematical session of the STEM for Britain event. An aim of STEM for Britain is to foster greater dialogue and engagement between early-stage researchers and Members both in Westminster and in their Constituencies. It was a valuable experience to discuss my research and explain its wider impact both with other researchers and the stakeholders present. |
Year(s) Of Engagement Activity | 2020 |
Description | Stem4Britain poster |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Policymakers/politicians |
Results and Impact | My PhD student Josephine Solowiej-Wedderburn was selected to present a poster at the STEM4Britain poster competition whose aim is to give members of the Houses of Parliament an new perspective of the the research going on in the UK in particular by early career researchers. Josephine presented work on our cell adhesion and mechanotransduction models looking at the cell-substrate interface, in particular its importance for tissue scaffold engineering and experimental design. |
Year(s) Of Engagement Activity | 2020 |
Description | eSMB 2020 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Gave a talk at the virtual eSMB conference to an international audience of research users (approximately 50 attended via zoom). This sparked discussions with some of the attendees following the talk and I was able to share a preprint of our work with them. |
Year(s) Of Engagement Activity | 2020 |