Molecular Force Imaging Reveals That Integrin-Dependent Mechanical Checkpoint Regulates Fcγ-Receptor-Mediated Phagocytosis in Macrophages

IF 9.1 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Yuru Hu, Hongyun Li, Wenxu Wang, Feng Sun, Chaoyang Wu, Wei Chen* and Zheng Liu*, 
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Abstract

Macrophages are a type of immune cell that helps eliminate pathogens and diseased cells. Recent research has shown that macrophages can sense mechanical cues from potential targets to perform effective phagocytosis, but the mechanisms behind it remain unclear. In this study, we used DNA-based tension probes to study the role of integrin-mediated forces in FcγR-mediated phagocytosis. The results showed that when the phagocytic receptor FcγR is activated, the force-bearing integrins create a “mechanical barrier” that physically excludes the phosphatase CD45 and facilitates phagocytosis. However, if the integrin-mediated forces are physically restricted at lower levels or if the macrophage is on a soft matrix, CD45 exclusion is significantly reduced. Moreover, CD47-SIRPα “don’t eat me” signaling can reduce CD45 segregation by inhibiting the mechanical stability of the integrin barrier. These findings demonstrate how macrophages use molecular forces to identify physical properties and combine them with biochemical signals from phagocytic receptors to guide phagocytosis.

Abstract Image

分子力成像揭示整合素依赖性机械检查点调控巨噬细胞fc γ-受体介导的吞噬作用
巨噬细胞是一种帮助消灭病原体和患病细胞的免疫细胞。最近的研究表明,巨噬细胞可以感知来自潜在目标的机械信号来进行有效的吞噬,但其背后的机制尚不清楚。在这项研究中,我们使用基于dna的张力探针来研究整合素介导的力在fc γ r介导的吞噬作用中的作用。结果表明,当吞噬受体FcγR被激活时,承受力的整合素产生“机械屏障”,物理排斥磷酸酶CD45,促进吞噬。然而,如果整合素介导的力在物理上被限制在较低的水平,或者巨噬细胞位于软基质上,CD45的排斥就会显著降低。此外,CD47-SIRPα“不要吃我”信号可以通过抑制整合素屏障的机械稳定性来减少CD45的分离。这些发现证明了巨噬细胞如何利用分子力来识别物理特性,并将其与来自吞噬受体的生化信号结合起来指导吞噬。
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来源期刊
Nano Letters
Nano Letters 工程技术-材料科学:综合
CiteScore
16.80
自引率
2.80%
发文量
1182
审稿时长
1.4 months
期刊介绍: Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.
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