# Target cell tension regulates macrophage trogocytosis

**Authors:** Caitlin E. Cornell, Aymeric Chorlay, Deepak Krishnamurthy, Nicholas R. Martin, Lucia Baldauf, Daniel A. Fletcher

PMC · DOI: 10.21203/rs.3.rs-5806746/v1 · 2025-02-05

## TL;DR

This study shows that the tension of a target cell's membrane influences whether macrophages trogocytose or phagocytose it.

## Contribution

The paper reveals that target cell cortical tension, not the macrophage, regulates trogocytosis versus phagocytosis.

## Key findings

- Low target cell tension promotes trogocytosis, while high tension favors phagocytosis.
- Macrophages can switch from trogocytosis to phagocytosis when membrane tension increases.
- A mechanical model explains how antibody density and cell stiffness affect this process.

## Abstract

Macrophages are known to engulf small membrane fragments, or trogocytose, target cells and pathogens, rather than fully phagocytose them. However, little is known about what causes macrophages to choose trogocytosis versus phagocytosis. Here, we report that cortical tension of target cells is a key regulator of macrophage trogocytosis. At low tension, macrophages will preferentially trogocytose antibody-opsonized cells, while at high tension they tend towards phagocytosis. Using model vesicles, we demonstrate that macrophages will rapidly switch from trogocytosis to phagocytosis when membrane tension is increased. Stiffening the cortex of target cells also biases macrophages to phagocytose them, a trend that can be countered by increasing antibody surface density and is captured in a mechanical model of trogocytosis. This work suggests that the target cell, rather than the macrophage, determines phagocytosis versus trogocytosis, and that macrophages do not require a distinct molecular pathway for trogocytosis.

## Full-text entities

- **Genes:** CD47 (CD47 molecule) [NCBI Gene 961] {aka IAP, MER6, OA3}, Fcr (Fc receptor) [NCBI Gene 109615], Cd47 (CD47 antigen (Rh-related antigen, integrin-associated signal transducer)) [NCBI Gene 16423] {aka 9130415E20Rik, B430305P08Rik, IAP, Itgp}, FCGR1A (Fc gamma receptor Ia) [NCBI Gene 2209] {aka CD64, CD64A, FCG1, FCGR1, FCRI, FcgammaRI}
- **Diseases:** bacterial infections (MESH:D001424), cancer (MESH:D009369), blood cancers (MESH:D019337)
- **Chemicals:** Lipid (MESH:D008055), NHS-biotin (MESH:C033788), indium tin oxide (MESH:C109984), glutaraldehyde (MESH:D005976), glucose (MESH:D005947), PC (MESH:D010767), 1640 RPMI (-), POPC (MESH:C028694), AF647 (MESH:C569686), glycine (MESH:D005998), Biotin (MESH:D001710), amines (MESH:D000588), chloroform (MESH:D002725), DSPE (MESH:C038089), rhodamine (MESH:D012235), Sucrose (MESH:D013395), reactive oxygen species (MESH:D017382), lissamine rhodamine phosphatidylethanolamine (MESH:C046703), PBS (MESH:D007854), CO2 (MESH:D002245), CMFDA (MESH:C069306), HI (MESH:D006639), LPS (MESH:D008070), Pen (MESH:C058388)
- **Species:** Entamoeba histolytica (species) [taxon 5759], C. elegans [taxon 328850], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Pseudomonas aeruginosa (species) [taxon 287]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232), HL60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002), Raji B — Homo sapiens (Human), EBV-related Burkitt lymphoma, Cancer cell line (CVCL_0511), J774A.1 — Mus musculus (Mouse), Mouse reticulum cell sarcoma, Cancer cell line (CVCL_0358), RAW — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_F681), Jurkat — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0065), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), Raji Bs — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_UY99)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11838726/full.md

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Source: https://tomesphere.com/paper/PMC11838726