The swarming behaviour of neutrophils in response to sites of local tissue damage has recently been characterised1, through protocols such as two-photon laser pulse-induced sterile skin injury and two-photon intravital imaging2,3. A few initial local 'pioneer' neutrophils responding to the resultant damage signals hone in on the site of tissue injury. This is followed by a mass migration of more distal neutrophils moving directly towards the damage site. These larger swarms can persist, or disband and reform at another nearby damage site. We seek to investigate the signalling factor dynamics that lead to this multi-stage swarming behaviour through computational simulation.
Our agent-based simulation technology4 explicitly represents each individual cell, its state and location in physical space. It permits a detailed manipulation and examination of cellular interactions with one another and their environments. Statistical profiles of neutrophil motility can be constructed and contrasted with similar profiles obtained from two photon intravital imaging data. Using this simulation technology we can represent the dynamics of different chemotactic signalling factors and their sources, and ascertain which best matches in vivo neutrophil motility patterns. We can examine the possible influences of the extracellular matrix and tissue structure, which may impede or restrict neutrophil movement, and the directionality of tissue cell lysis on neutrophil motility.
We ensure our simulations are biologically accurate and relevant through a principled simulation development process4,5. This process maintains explicit records of assumptions and links simulation artefacts to biological literature and data, and constructs a logical argument (the type employed in, e.g., arguing aircraft are safe to fly) supporting the simulation's appropriate capture of the biology.