Irregular particle morphology and membrane rupture facilitate ion gradients in the lumen of phagosomes

Maksim V Baranov; Melina Ioannidis; Sami Balahsioui; Auke Boersma; Rinse de Boer; Manoj Kumar; Masato Niwa; Tasuku Hirayama; Qintian Zhou; Terrence M Hopkins; Pieter Grijpstra; Shashi Thutupalli; Stefano Sacanna; Geert van den Bogaart

doi:10.1016/j.bpr.2022.100069

Irregular particle morphology and membrane rupture facilitate ion gradients in the lumen of phagosomes

Biophys Rep (N Y). 2022 Aug 11;2(3):100069. doi: 10.1016/j.bpr.2022.100069. eCollection 2022 Sep 14.

Authors

Affiliations

¹ Department of Molecular Immunology, 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 nternational Centre for Theoretical Sciences, Tata Institute of Fundamental Research, Bangalore, India.
⁶ Department of Medical Biology and Pathology, University Medical Center Groningen, Groningen, Netherlands.

Abstract

Localized fluxes, 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, together with localized membrane rupture, suffice 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 nearer to the cores of the particles. Our study strengthens the concept that coupling metabolic and signaling reaction cascades can be spatially confined by localized limited diffusion.