WP2

WP2

Mechanobiological Models of Cell-Cell and Cell-ECM interactions

The tissue microenvironment influences cell functionality. How cells maintain and remodel the extracellular matrix (ECM) is  vitally  important  both  for  tissue  homeostasis  and  for  pathological  scenarios  such  as  tumour growth, cancer invasion and myocardial infarction (MI).

Project 1: We will adopt an individual-based, force-based modelling approach to investigate cell-cell, cell-fibre and cell-ECM interactions using our multiscale-multicompartment model.

Project2:  By taking into account the results of WP1 concerning the biomechanical properties of the cells and including the effect of actin and integrins on cell-ECM adhesion, we will develop a new system of intracellular ODEs governing these dynamics.

Project3:  model extension through computational upscalling

Project4:  Development of a fully 3D multiscale computational model of a growing, invading cell mass, which will be applied to the specific cases of breast cancer through WP6

Team: Prof. Chaplain (Team leader), Dr. McDougall, Prof. Ogden, Dr. Yin, Prof. Olson, Prof. Insall,
Prof. Husmeier, Prof. Luo, PDRA2, PhD2, PhD3 

Progress

We have developed a 3D computational code which is being used as the basis to simulate the force-based, individual-based model of cell-cell, cell-matrix and cell-blood-vessel interactions.

The model has now been implemented to model the growth of cancer cells around a central blood vessel - the “tumour cord” or “tumour cuff”. In this scenario, tumour cells grow around a central blood vessel with those cells further away from the blood vessel experiencing lower nutrient levels. The work carried out here was the first to adopt an individual-based model to examine the growth of tumour cords and was able to estimate the distance from the blood vessel that cancer cells first became necrotic.

The new code has also been extended to include individual fibres in 3-dimensions and thus enable the explicit modelling of cell-matrix interactions. This will be used for the basis of a model of cancer invasion of the extracellular matrix (ECM) as well as for the first simulations of myocardial infarction. Additionally we have extended the code to solve numerically PDEs in 3D and thus provide the computational solution to external chemical fields, such as oxygen. This has been done in such a way as to be compatible and integrable with the software being developed in WP6 by Professor McDougall and the initial modelling of perfusion already carried out there. In parallel, we have developed computational method and experimental studies on cell migration and chemotaxis.

MCWP2Fig1sizedMCWPFig2resized