Physical confinement and phagocytic uptake induce persistent cell migration
Summer G Paulson1,2, Sophia Liu1,2, Jeremy D Rotty1
1Uniformed Services University of the Health Sciences, Department of Biochemistry, Bethesda, MD, USA, 20814.
Biology Open
|September 1, 2025
Summary
Physical confinement significantly enhances phagocytosis in BV2 microglia-like cells, acting as a potent driver. This effect involves the Arp2/3 complex and myosin II, influencing cell migration and immune responses.
Area of Science:
- Cell Biology
- Immunology
- Biophysics
Background:
- Phagocytosis is typically studied in unconfined in vitro settings.
- The influence of physical confinement on phagocytosis is not well understood.
- Microglia play a critical role in the innate immune response.
Purpose of the Study:
- To investigate the impact of physical confinement on IgG-mediated phagocytosis in BV2 microglia-like cells.
- To elucidate the cytoskeletal mechanisms underlying confinement-modulated phagocytosis and cell migration.
- To explore the phenomenon of 'phagocytic priming' and its dependence on confinement and cell adhesion.
Main Methods:
- Utilized BV2 microglia-like cells in both confined and unconfined in vitro assays.
- Investigated IgG-mediated phagocytosis using fluorescent beads.
- Examined the roles of Arp2/3 complex, myosin II, and integrin-dependent adhesion using pharmacological inhibitors and genetic disruption.
- Assessed cell migration and 'phagocytic priming' using live-cell imaging.
Main Results:
- Physical confinement significantly increased the fraction of phagocytic cells compared to unconfined conditions.
- Confinement partially rescued phagocytic uptake upon myosin II disruption and conferred partial resistance to cytochalasin D.
- Bead uptake stimulated persistent cell migration, termed 'phagocytic priming', which required integrin-dependent adhesion.
- Cytoskeletal requirements for phagocytic priming differed between confined (Myosin II, Arp2/3 complex required) and unconfined settings.
Conclusions:
- Physical confinement is a potent enhancer of phagocytosis in microglia.
- Confinement alters the cytoskeletal dynamics of phagocytosis and phagocytic priming.
- Phagocytic priming, modulated by confinement, may be a key innate immune mechanism for wound surveillance.
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