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

TL;DR

This study introduces a Monte Carlo membrane simulation framework to explore how the mechanical properties of soft, deformable targets influence phagocytosis, revealing distinct regimes of engulfment and displacement relevant to immune responses.

Contribution

The paper develops a novel simulation approach to model phagocytosis involving flexible membranes, highlighting the role of target deformability in determining engulfment outcomes.

Findings

Identified three mechanical regimes: biting, pushing, and full engulfment.

Demonstrated that membrane tension influences transition between regimes.

Supported simulation results with experiments on GUVs and lymphoma cells.

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.