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Updated: May 5, 2026
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Microneedle-Based Analysis Reveals Polarity-Dependent Spatial Regulation of Macrophage Phagocytosis
Dan Horonushi1, Haruka Yuki1, Kaho Noumi2
1Department of Pure and Applied Physics, Graduate School of Advanced Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku, Tokyo 169-8555, Japan.
Abstract:
Phagocytosis and migration in macrophages share key regulators, including Rho family GTPases; however, whether phagocytic membrane extension generates a transient, whole-cell polarity that coordinates migration and spatial prioritization of engulfment remains unclear. Here, we investigated the spatiotemporal coupling between membrane extension and cell migration using opsonized microneedles, which enable controlled stimulation together with long-range membrane extension and backtracking dynamics. During single-needle stimulation, membrane extension was tightly coupled to directional migration, whereas membrane retraction showed weaker coupling. In sequential stimulation with two microneedles, ongoing phagocytosis suppressed competing membrane extension at spatially opposite locations, and a reversal in migration direction was accompanied by initiation of membrane extension toward the second needle. Third-needle experiments further revealed a polarized spatial distribution of phagocytic responsiveness across the cell surface. Consistently, uniform stimulation with multiple opsonized microbeads demonstrated sequential, one-at-a-time engulfment even under near-simultaneous target attachment. These results support a model in which phagocytic membrane extension establishes transient, whole-cell polarity that spatially gates engulfment and coordinates whole-cell migration. The microneedle manipulation platform provides a powerful approach for dissecting the spatiotemporal regulation of phagocytosis and for understanding macrophages as adaptive living micromachines integrating mechanical inputs, transient polarity formation, and sequential target processing.
Insights
Macrophages use membrane extension during phagocytosis to create temporary cell polarity, guiding migration and prioritizing engulfment. This coordinated process ensures sequential target processing, even with multiple targets.
Area of Science:
- Cell Biology
- Immunology
- Biophysics
Background:
- Phagocytosis and cell migration in macrophages share regulatory pathways, notably Rho family GTPases.
- The role of phagocytic membrane extension in establishing transient, whole-cell polarity for coordinated migration and engulfment remains poorly understood.
Purpose of the Study:
- To investigate the spatiotemporal coupling between membrane extension during phagocytosis and macrophage migration.
- To determine if phagocytic membrane extension generates transient whole-cell polarity that influences migration and engulfment prioritization.
Main Methods:
- Utilized opsonized microneedles for controlled, long-range stimulation of macrophages, enabling analysis of membrane extension and retraction dynamics.
- Employed sequential and simultaneous stimulation with microneedles and microbeads to assess spatial and temporal regulation of phagocytosis and migration.
Main Results:
- Membrane extension during single-needle stimulation was tightly coupled to directional migration.
- Ongoing phagocytosis suppressed membrane extension at other locations, and migration reversals were linked to new membrane extension.
- Macrophages exhibited polarized phagocytic responsiveness, engulfing targets sequentially even when multiple were attached simultaneously.
Conclusions:
- Phagocytic membrane extension establishes transient, whole-cell polarity that spatially regulates engulfment and coordinates cell migration.
- Macrophages act as adaptive micromachines integrating mechanical cues, polarity formation, and sequential target processing.
- The microneedle platform is effective for studying the spatiotemporal regulation of phagocytosis and macrophage behavior.
