A biophysical model of phagocytic cup dynamics: The effect of membrane tension

Author summary Phagocytosis is the vital process by which specialised immune cells, such as macrophages, engulf and destroy marked targets such as bacteria, dead cells, or even cancer cells. While this is a cornerstone of our immune defence, the physical forces that govern how a cell stretches its membrane around a target remain difficult to experimentally measure. We developed a new mathematical framework to explore how “membrane tension,” the physical resistance to stretching the cell’s surface, impacts this engulfment. We found that as a cell wraps around a target, rising tension acts like a mechanical brake, slowing the process down or even causing it to stop entirely, a phenomenon known as frustrated phagocytosis. However, our model also shows that cell signalling pathways can overcome this resistance by effectively relaxing the membrane, allowing the cell to complete the job quickly and efficiently. By identifying a specific mechanical window of target sizes that a cell can successfully ingest, our work provides fresh insights into how immune cells interact with their environment. These findings could eventually help scientists design more effective drug delivery systems or better understand underlying biology of how certain pathogens manage to evade the immune system’s reach.