Kinetics of phagosome maturation is coupled to their intracellular motility

Kinetics of cargo degradation in phagosomes are measured through engineered RotSensors, capturing their translational and rotational dynamics in parallel. Immune cells degrade internalized pathogens in phagosomes through sequential biochemical changes. The degradation must be fast enough for effective infection control. The presumption is that each phagosome degrades cargos autonomously with a distinct but stochastic kinetic rate. However, here we show that the degradation kinetics of individual phagosomes is not stochastic but coupled to their intracellular motility. By engineering RotSensors that are optically anisotropic, magnetic responsive, and fluorogenic in response to degradation activities in phagosomes, we monitored cargo degradation kinetics in single phagosomes simultaneously with their translational and rotational dynamics. We show that phagosomes that move faster centripetally are more likely to encounter and fuse with lysosomes, thereby acidifying faster and degrading cargos more efficiently. The degradation rates increase nearly linearly with the translational and rotational velocities of phagosomes. Our results indicate that the centripetal motion of phagosomes functions as a clock for controlling the progression of cargo degradation.

Automated summary

Using engineered RotSensors, we discovered that the degradation kinetics of individual phagosomes are not random, but rather linked to their intracellular motion. Faster and more rotational phagosomes are more likely to fuse with lysosomes, resulting in more efficient cargo degradation. This suggests that the motion of phagosomes plays a crucial role in controlling the progression of cargo degradation.