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Phagocytosis is the fundamental cellular process by which eukaryotic cellsbind and engulf particles by their cell membrane. Particle engulfment involvesparticle recognition by cell-surface receptors, signaling and remodeling of theactin cytoskeleton to guide the membrane around the particle in a zipper-likefashion. Despite the signaling complexity, phagocytosis also depends stronglyon biophysical parameters, such as particle shape, and the need foractin-driven force generation remains poorly understood. Here, we propose anovel, three-dimensional and stochastic biophysical model of phagocytosis, andstudy the engulfment of particles of various sizes and shapes, including spiraland rod-shaped particles reminiscent of bacteria. Highly curved shapes are nottaken up, in line with recent experimental results. Furthermore, wesurprisingly find that even without actin-driven force generation, engulfmentproceeds in a large regime of parameter values, albeit more slowly and withhighly variable phagocytic cups. We experimentally confirm these predictionsusing fibroblasts, transfected with immunoreceptor FcyRIIa for engulfment ofimmunoglobulin G-opsonized particles. Specifically, we compare the wild-typereceptor with a mutant receptor, unable to signal to the actin cytoskeleton.Based on the reconstruction of phagocytic cups from imaging data, we indeedshow that cells are able to engulf small particles even without support frombiological actin-driven processes. This suggests that biochemical pathwaysrender the evolutionary ancient process of phagocytic highly robust, allowingcells to engulf even very large particles. The particle-shape dependence ofphagocytosis makes a systematic investigation of host-pathogen interactions andan efficient design of a vehicle for drug delivery possible.

The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape