Communication through autoattractants can enhance and limit collective migration of immune cells

Abstract

Many eukaryotic cells produce attractant molecules to which they themselves are also attracted. For example, neutrophils produce leukotriene B4 while swarming. These autoattractants create a secondary signalling layer that can coordinate collective cell behaviour during chemotaxis. Here we use a hybrid agent-based computational model to examine how immune cells migrating along a self-generated gradient may communicate with each other using autoattractants. We find that autoattractant signals strongly enhance cells' responses to primary attractant. Efficient removal of autoattractants is also crucial, through depletion by cells, chemical instability, or enzymatic breakdown. Consequently, autoattractants have a lifetime, determined by a balance between production and removal rates. We find that optimal lifetimes exist, and that these are determined by cell speed and attractant diffusion, but are remarkably independent of cell density and primary attractant concentration. We further show that autoattractants whose removal is governed by inherent instability rather than breakdown by cells coordinate migration less efficiently, but work more robustly across different environments. Finally, we find that autoattractant signalling without direct breakdown by the cells involved establishes a characteristic optimal cell-cell distance: too little communication leaves cells uncoordinated, while excessive communication causes cells to aggregate into slow-moving clumps. Strikingly, the conditions that produce optimal chemotaxis lie very close to those that trigger aggregation, suggesting that many autoattractant systems operate near a critical boundary.