BPS2026 – Messy eaters: Mechanisms of trogocytic membrane exchange in macrophages

Trogocytosis (Trogo- Greek, “to nibble”), or the selective engulfment of small “bites” from a target cell, has emerged in the last twenty years as a common but poorly understood process in diverse cell types and species. For example, trogocytosis has been observed during tissue homeostasis, brain development, stem cell differentiation, and pathogenesis. Trogocytosis has also been implicated in the exchange of surface proteins. Macrophages exchange surface proteins with hematopoietic stem cells in the bone marrow, restricting their egress into the bloodstream. Recently, we discovered that the decision by a macrophage to phagocytose or trogocytose a cancer cell is governed by the target itself. Through experiments with antibody-labeled cells and membrane-only cell mimics, we found that macrophages preferentially engulf stiff cells but nibble soft ones. We demonstrated that trogocytic efficiency of antibody-labeled cells depends on target cortical tension and the density of antibodies coating the target cell surface, a concept we captured in a mechanical model of macrophage trogocytosis. One striking outcome of trogocytosis is “cross-dressing,” where a macrophage that takes a bite from a target cell can display proteins from the target on its plasma membrane. Here, we demonstrate that trogocytosis often, but not always, leads to cross-dressing on the macrophage membrane. We quantify the cellular and biophysical parameters that drive membrane exchange between target cells and macrophages using a combination of flow cytometry, high-resolution confocal microscopy, and focused ion beam scanning electron microscopy. Our work suggests that trogocytosis and cross-dressing by macrophages are both influenced by the biophysical properties of the target cell-macrophage interface.