Published November 8, 2021 | Version 1
Journal article Open

Close membrane apposition facilitates ion gradients in the lumen of phagosomes

  • 1. Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Groningen, Netherlands
  • 2. Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India
  • 3. Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, 1–25–4, Daigaku-nishi, Gifu 201–1196, Japan
  • 4. Molecular Design Institute, Department of Chemistry, New York University, New York, NY, United States
  • 5. International Centre for Theoretical Sciences, Tata Institute of Fundamental Research, Bangalore, India
  • 6. 1. Department of Molecular Immunology and Microbiology, Groningen Biomolecular Sciences and Biotechnology Institute, University oGroningen, Groningen, Netherlands

Description

Localized flux, production and/or degradation coupled to limited diffusion are well-known to result in stable spatial concentration gradients of biomolecules in the cell. In this study, we demonstrate that this also holds true for small ions, since we found that the close membrane apposition between the membrane of a phagosome and the surface of the cargo particle it encloses, suffices for stable gradients of protons and iron cations within the lumen of the phagosome. Our data show that in phagosomes containing hexapod-shaped silica colloid particles, the phagosomal membrane is ruptured at the positions of the tips of the rods, but not at other positions. This results in the confined leakage at these positions of protons and iron from the lumen of the phagosome into the cytosol. In contrast, acidification and iron accumulation still occur at the positions of the phagosomes of the cores of the particles. Our study strengthens the concept that the coupling of metabolic and signaling reaction cascades can be spatially confined by localized limited diffusion.

Notes

ST, SS and GB are funded by a Young Investigator Grant from the Human Frontier Science Program (HFSP; RGY0080/2018). GB has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 862137) and the Netherlands Organization for Scientific Research (Vidi grant NWO-ALW VIDI 864.14.001). ST further acknowledges support from the Department of Atomic Energy, Government of India, under project no. 12-R&D-TFR-5.04-0800 and 12-D&D-TFR-5.10-1100, the Simons Foundation (Grant No. 287975) and the Max Planck Society through a Max-Planck Partner-Group.

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