Mathematical investigation into the role of cell-cell communication pathways on collective cell migration

A large number of fundamental processes in development and various diseases (e.g., cancer growth and invasion, wound healing, morphogenesis) are the result of the coordinated movement of cells. Independent of cell types, collective movement usually involves three factors: cell-cell and cell-matrix interactions, polarization of cells into "leaders" and "followers", and chemical and physical signals that allow cells to communicate with each other. There are multiple ways of cell movement, ranging from single cell movement to collective movement (where cells stay connected as they move).

The movement of single cells has been investigated quite in detail over the past decades, and the key aspects of single cell movement (e.g., molecular control of cell protrusions, interactions between cells and their substrate) have been already identified. However, the collective movement of cells is less understood, and there are many open questions regarding the mechanisms involved in this type of movement. For example, it is less understood how cell movement and cell-cell communication interact to create new tissues, or to allow cells to colonise specific areas. Another aspect less understood is how cells interpret and integrate signals from the environment and from other cells to produce specific types of cell aggregations and collective movement. Finally, it is still unknown whether all cells sense guidance signals, or only the leader cells sense these signals and then instruct other cells to follow them.

To formulate hypotheses that could help address these questions, we will derive a class of mechanistic mathematical models that describe cell movement and cell-cell interactions via different communication mechanisms. Using various mathematical techniques (e.g. travelling wave analysis, bifurcation analysis), we will investigate the role of different cell-cell communication mechanisms on the movement and structure of cell aggregations. We will also investigate the effect of parameters on the transitions between different types of cell movement behaviours.

The proposed research will achieve its impact through the application of modelling and techniques developed here to investigate experimental data on cell-cell signalling and cell migration, and to propose new experimental hypotheses.

At this stage, the research has a predominantly academic impact (with immediate beneficiaries being other researchers in cell biology and applied mathematics). However, the impact will be broadened by the set up of new collaborations and further grant applications that could take these ideas further for business exploitation (especially in the biotechnical industry, where cell migration is becoming very important in the context of artificial tissues and stem cell implants). To this end, in the first year I will be looking to apply for other grants that can take the ideas developed during this grant period further to the market (e.g., the EPSRC Follow On Fund, Technology Strategy Board initiatives, the MRC Developmental Pathway Funding Scheme). Also, during this first grant stage I intend to look at suitable industrial collaborative partners, as my research will develop for longer-term collaborations. Examples of possible industrial partners in Scotland are DySIS Medical or Mode Diagnostics.

In the short term, this research is expected to lower the costs and shorten the time period for basic experiments on cell migration. This could reduce the time for treatments (for cancers and developmental diseases) to go from the bench to the bedside. Also, it could increase the effectiveness of current treatments by better understanding the mechanisms of the diseases.

In the long term, progress in the design of new treatments is expected to have economic and commercial benefits through exploitation of this research by the large pharmaceutical companies, which contribute significantly to the UK prosperity. It is also expected that the success of this project will enhance the quality of life patients.


The results of this proposed research will be disseminated in leading academic journals, and at conferences in the mathematical biology and applied mathematics fields. Also, the results will be disseminated in the annual Newsletter of the Division of Mathematics, University of Dundee.

Finally, this project creates the opportunity for training a new Postdoctoral Fellow with interdisciplinary relevant skills. The Fellow will acquire knowledge in both applied mathematics and cell biology, and will learn to integrate concepts and methods from these different disciplines. This can prepare the Postdoctoral Fellow for a wider range of employment.