Depierre Manon, Mularski Anna, Ruppel Artur, Le Clainche Christophe, Balland Martial, Niedergang Florence
Université Paris Cité, Institut Cochin, INSERM, CNRS, 75014 Paris, France.
Université Grenoble Alpes, CNRS, Interdisciplinary Laboratory of Physics (LIPhy), Grenoble, France.
iScience. 2025 Feb 20;28(4):112067. doi: 10.1016/j.isci.2025.112067. eCollection 2025 Apr 18.
Phagocytosis is the process of actin-dependent internalization and degradation of large particles. Macrophages, which are professional phagocytes, are present in all tissues and are, thus, exposed to environments with different mechanical properties. How mechanical cues from macrophages' environment affect their ability to phagocytose and, in turn, how phagocytosis influences how phagocytic cells interact with their environment remain poorly understood. We found that the ability of macrophages to perform phagocytosis varied with the substrate stiffness. Using live traction force microscopy, we showed that phagocytosing macrophages applied more dynamic traction forces to their substrate. In addition, integrin-mediated phagocytosis triggered a transient loss of podosomes that was associated with decreased degradation of the extracellular matrix, concomitantly with RhoA activation and F-actin recruitment at phagocytic cups. Overall, these results highlight a crosstalk between macrophage phagocytosis and cell adhesion. Mechanical properties of the microenvironment influence phagocytosis, which, in turn, impacts how macrophages interact with their surroundings.
吞噬作用是肌动蛋白依赖的大颗粒内化和降解过程。巨噬细胞作为专职吞噬细胞，存在于所有组织中，因此会接触到具有不同力学性质的环境。巨噬细胞所处环境的力学信号如何影响其吞噬能力，以及反过来吞噬作用如何影响吞噬细胞与周围环境的相互作用，目前仍知之甚少。我们发现巨噬细胞的吞噬能力随底物硬度而变化。使用活细胞牵引力显微镜，我们发现正在进行吞噬的巨噬细胞会对其底物施加更多动态牵引力。此外，整合素介导的吞噬作用会引发足体的短暂丧失，这与细胞外基质降解减少有关，同时在吞噬杯处伴随RhoA激活和F-肌动蛋白募集。总体而言，这些结果突出了巨噬细胞吞噬作用与细胞黏附之间的相互作用。微环境的力学性质影响吞噬作用，而吞噬作用又会影响巨噬细胞与周围环境的相互作用方式。
