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

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.

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PubMed
Published
2026-01-28
Primary Topic
Cellular Mechanics and Interactions
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article
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article

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

Valentin Jaumouillé, Shubhadeep Sadhukhan, Caitlin E. Cornell, Daan Vorselen et al.
PubMed
Cellular Mechanics and Interactions
article

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

Valentin Jaumouillé, Shubhadeep Sadhukhan, Caitlin E. Cornell, Daan Vorselen, Youri Peeters, Nir S. Gov, Mansehaj Kaur Sandhu, Daniel A Fletcher, Samo Penič, Aleš Iglič
article en

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.

PubMed
Lawrence Berkeley National Laboratory (US), University of Ljubljana (SI), Simon Fraser University (CA), University of California, San Francisco (US), University of Cambridge (GB), Chan Zuckerberg Initiative (United States) (US), Weizmann Institute of Science (IL), Wageningen University & Research (NL), University of California, Berkeley (US)
Openalex Percentile: Top 66%
Cellular Mechanics and Interactions
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