From biting to engulfment: curvature–actin coupling controls phagocytosis of soft, deformable targets

Abstract Phagocytosis is a fundamental process of the innate immune system, yet the physical determinants that govern the engulfment of soft, deformable targets remain poorly understood. Existing theoretical models typically approximate targets as rigid particles, overlooking the fact that both immune cells and many biological targets undergo significant membrane deformation during contact. Here, we develop a Monte Carlo–based membrane simulation framework to model the interactions of multiple vesicles, enabling us to explore phagocytosis-like processes in systems where both the phagocyte and the target possess flexible, thermally fluctuating membranes. We first validate our approach against established observations for the engulfment of rigid objects. We then investigate how the mechanical properties of a soft target—specifically membrane bending rigidity govern the outcome of phagocytic interactions. Our simulations reveal three distinct mechanical regimes: (i) biting or trogocytosis, in which the phagocyte extracts a portion of the target vesicle; (ii) pushing, where the target is displaced rather than engulfed; and (iii) full engulfment, in which the target is completely internalized. Increasing membrane tension via internal pressure produces analogous transitions, demonstrating a unified mechanical origin for these behaviours. Qualitative comparison with experiments involving Giant Unilamellar Vesicles (GUVs, deformable microparticles) and lymphoma cells supports the relevance of these regimes to biological phagocytosis. Together, these results highlight how target deformability fundamentally shapes phagocytic success and suggest that immune cells may exploit mechanical cues to recognize among different classes of soft targets. Significance statement Phagocytosis is essential for immune defence, yet the physical principles governing the engulfment of soft, deformable targets remain poorly understood. Most theoretical models assume rigid particles, even though real cells undergo substantial shape changes during contact. Here, we develop a theoretical membrane model to simulate interactions between multiple vesicles, enabling a mechanistic exploration of phagocytosis of soft targets. We show that target membrane rigidity dictates whether it is fully engulfed, pushed away, or partially bitten. These mechanically driven regimes explain experimental observations of immune cells engaging with both artificial GUVs and lymphoma cells. Competing Interest Statement The authors have declared no competing interest.