Reduction of Nanoparticle Load in Cells by Mitosis but Not Exocytosis

Abstract

The long-term fate of biomedically relevant nanoparticles (NPs) at the single cell level after uptake is not fully understood yet. We report that lysosomal exocytosis of NPs is not a mechanism to reduce the particle load. Biopersistent NPs such as nonporous silica and gold remain in cells for a prolonged time. The only reduction of the intracellular NP number is observed via cell division, e.g., mitosis. Additionally, NP distribution after cell division is observed to be asymmetrical, likely due to the inhomogeneous location and distribution of the NP-loaded intracellular vesicles in the mother cells. These findings are important for biomedical and hazard studies as the NP load per cell can vary significantly. Furthermore, we highlight the possibility of biopersistent NP accumulation over time within the mononuclear phagocyte system.

Asymmetry of nanoparticle inheritance upon cell division: Effect on the coefficient of variation

“…Given the interest in asymmetric nanoparticle inheritance, we posed the question whether there exist simple, high-throughput, experiments that could explicitly measure or at least give an indication of the degree of asymmetry even without detailed mathematical modelling [13][14][15][16]18,20] or tedious tracking of single cells [19][20][21][22]. We have previously argued, both from a theoretical perspective [24] as well as with simulations [23], that the mean nanoparticle uptake https://doi.org/10.1371/journal.pone.0242547.g001…”

“…In this context, it has repeatedly been observed that when cells divide, the nanoparticles they have taken up are shared between the resulting daughter cells in an asymmetrical fashion [12][13][14][15][16][17][18][19][20][21][22], that is, one daughter cell receiving more of the nanoparticles from the mother than the other daughter cell. Evidence for such an asymmetry includes fits of computational [13,14] and theoretical [15,16,20] models to experimental data, as well as more direct observations by tediously imaging individual cells as they divide and subsequently tracking the nanoparticle inheritance pattern of the daughter cells [19][20][21][22].…”

Quantitative Particle Uptake by Cells as Analyzed by Different Methods

“…Particles may be also released from endosomes/lysosomes to the extracellular medium by exocytosis . Exocytosis of particles is however strongly size‐dependent, and thus is not always an efficient pathway for particle clearance from cells . Apart from particle uptake by endocytosis there are thus several pathways leading to the reduction of the number of intracellular particles.…”

Analyse quantitativer Partikelaufnahme von Zellen über verschiedene Messmethoden

“…Partikel könnten auch aus den Endosomen/Lysosomen in das extrazelluläre Medium (ECM) durch Exozytose freigesetzt werden . Exozytose von Partikeln ist sehr stark größenabhängig und deshalb nicht immer ein effizienter Weg für Partikelfreisetzung aus Zellen . Neben einer Partikelaufnahme über Endozytose gibt es daher mehrere Wege, die zu einem Verlust der Anzahl von intrazellulären Teilchen führen.…”