Speaker
Description
Macrophages play an important role in the body's innate immune system. They digest smaller external threats, promote healing of internal wounds, and recruit other macrophages using chemokines (chemical signals).
These chemokines bind to specialised receptors on the cell membrane that trigger downstream signals. The receptor CXCR3 in macrophages, for example, is activated by the chemokines CXCL9 and CXCL11. These signals activate membrane-bound phospholipids, which recruit actin remodelling proteins to the cell wall. These membrane lipids can therefore act as a "compass" that point towards the chemical signal and guide the direction of cell motility.
The membrane lipids appear to "lock in" the upstream signal by limiting the ability to change course. How quickly does a macrophage identify the direction of chemotaxis? How does a macrophage respond to competing or conflicting chemotaxis signals? What chemokine concentration is required to override an existing signal?
To answer these questions, we developed a mathematical and computational model of macrophage chemotaxis that combines the internal signalling network cascades with a model of spatially diffused chemokines. We use this model to compare chemotaxis performance under different parameter values and initial conditions. In particular, we measure the relative strength and efficiency of each signal and the persistence of chemotactic movement in the presence of conflicting signals.
