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

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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.