Biological & Soft Matter Seminar: Phagocytosis is powered by actin “teeth” protrusive forces and myosin-II dependent constriction

Zoom: https://tau-ac-il.zoom.us/j/88904888353?pwd=dDIwaXRxSjlsVElkR0dXdTNPTGhnZz09

Abstract: 

Phagocytosis, the uptake of solid particles by cells, allows our immune cells to respond to widely differing threats, from invading microbes during infection to damaged and malignant cells in tissue homeostasis. These phagocytic targets differ greatly in their physical properties, such as their size, shape and rigidity. How macrophages adapt phagocytic mechanisms to robustly internalize targets with such diverse physical properties is unknown. To address this question, we recently developed a particle-based force microscopy method that allows us to precisely probe the interaction between phagocytes and their targets. In this approach, we synthesize highly tuneable and deformable hydrogel microparticles and functionalize them to trigger phagocytosis by macrophages. Deformations of these targets during uptake can be resolved with super resolution accuracy after conventional imaging and allows us to infer phagocytic forces. This approach reveals unexpected and spatially complex force exertion patterns in phagocytosis, and shows how phagocytosis is distinctly driven by a myosin-II powered contractile mechanism and individual Arp2/3-based actin structures (“teeth”). Most recently, we harnessed the high tunability of hydrogel microparticles for genome-wide identification of target-specific regulators of phagocytosis. Together, these results provide an unprecedented quantitative look at phagocytosis and challenge the current models for cellular internalization.