Phagocytosis is a key biological process involved both in immunity and tissues homeostasis, where immune cells ingest and degrade targets ranging from pathogens to apoptotic cells. This process requires rapid cytoskeleton reorganization and spatially controlled force generation as the particle is progressively engulfed by the cell. While model systems like gel beads have advanced our understanding of the underlying mechanisms and signaling pathways, they present limitations for fully capturing the mechanobiology of phagocytosis. Here, we propose to use oil-in-water droplets with controlled size as force sensors during engulfment. These particles are deformable and can be functionalized with ligands designed to target specific cellular receptors, enabling precise modulation of cell-droplet interactions. Importantly, their liquid-liquid interface allows these ligands to diffuse laterally at the surface and respond to the receptor clustering during recognition. Their deformability and known surface tension make them a relevant tool to study mechanical interactions as deformations directly reflect the normal stresses exerted during internalization. Using RAW 264.7 macrophages, we analyzed multiple phagocytic events. Statistical analysis demonstrated that droplet deformation is correlated with Fcγ receptor engagement and IgG recruitment. Epifluorescence microscopy revealed the dynamic progression of actin protrusions along the droplet surface during phagocytosis, highlighting distinct deformation patterns at different stages of the process. Combining confocal microscopy with computational modeling method, we reconstructed the three-dimensional shape of the droplets throughout engulfment and quantified the mechanical stresses acting on them at each point of their surface. We conclude that functionalized emulsion droplets constitute a powerful and versatile tool for probing the mechanobiology of phagocytosis. This approach provides new insight into how immune cells regulate force generation during target internalization and establishes a broadly applicable platform for studying receptor-mediated uptake in diverse contexts.
Uhl et al. (Sun,) studied this question.