A biophysical model of intracellular distribution and perinuclear accumulation of particulate matter

Abstract

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Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways

“…These lipids droplets are hypothesized to sequester toxicants in order to protect cells from unwanted toxicity. This hypothesis is supported by various in vitro studies on engineered nanoparticles that consistently show sequestration of nanoparticles in cytoplasmic bodies (which may include lipid droplets) in human alveolar cells, primary monocytes, and lung epithelial and monocyte‐derived macrophages from pulmonary cells [Lee et al, ; Rivolta et al, ; Sund et al, ]. These studies, together with the current analysis of whole air exposure, suggest that exposure to PM in urban/industrial air triggers changes in the transcription of genes implicated in lipid droplet formation.…”

The effect of nanoparticle uptake on cellular behavior: disrupting or enabling functions?

“…The other possibility is that NP uptake occurs by passive processes and the intracellular trafficking utilizes some energy gradients preexisting inside the cells, due to cell structure itself (cytoskeleton). 37 In other words, NP management may either amplify the cell request for energy or saturate the preexisting routes. These aspects must be taken into consideration regardless of the widespread idea of cytotoxicity.…”

“…According to the physicochemical characteristics of the nanocarrier and the nature of the target cells, two main internalization pathways may occur: either a non-energy-dependent interaction with plasma membrane 21,37 or the energy-dependent, endocytotic pathways 4 (see Figures 1 and 2). As far as the non-energy-dependent pathway is concerned, we have demonstrated that coumarin solid-lipid NPs (SLNs) interact with the plasma membrane after a few minutes of exposure.…”

“…45 In general, after cellular uptake, exogenous material of various origins tends to accumulate in the perinuclear region. 21,[46][47][48] This accumulation is against a diffusion gradient and favored probably by a local energy generated by the cytoskeleton dynamics, 37 suggesting that the integrity of the actin filaments may play a role in the intracellular distribution of NPs, maybe generating a force that helps the concentration of the substance in the perinuclear region.…”

Nanodiamonds coupled with 5,7-dimethoxycoumarin, a plant bioactive metabolite, interfere with the mitotic process in B16F10 cells altering the actin organization

“…45 Velasco-Velázquez et al 46 demonstrated that the coumarin derivative 4-hydroxycoumarin was able to disorganize cytoskeletal actin in B16F10 melanoma cells without altering its gene expression. Moreover, recently it was shown 47 that the fluorophore coumarin-6 coupled with solid lipid nanoparticles was able to penetrate in A30 human alveolar cells and spread out in the cytoplasm depending on the actin cytoskeletal structure, suggesting the possible physicochemical affinity and the consequent direct interaction between coumarin compounds and actin. All these evidences confirmed our results and encouraged us to propose the following action model of ND + C treatment in B16F10 cells ( Figure S3): NDs regulate the internalization of citropten in the cells, allowing C to reach low intracellular concentration not sufficient to induce apoptosis.…”