Ζ potential evidences silanol heterogeneity induced by metal contaminants at the quartz surface: Implications in membrane damage

Pavan, Cristina; Turci, Francesco; Tomatis, Maura; Ghiazza, Mara; Lison, Dominique; Fubini, Bice

doi:10.1016/j.colsurfb.2017.06.012

Cited by 17 publications

(13 citation statements)

References 46 publications

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“…The zeta potential of particles (ELS, measured in the various medium at specific pH), here used to describe the average acidity of surface silanols (Pavan et al 2017 ), acidic moieties with a potential for H-bonding, showed no significant differences among the set of samples, for the same medium. As expected, the zeta potential of particles dispersed in saline (0.01 M NaCl) at pH 4.5, which represents the lysosomal pH, was strongly negative (< − 40 mV).…”

Section: Resultsmentioning

confidence: 99%

“…These differences were assigned to the different average acidity of the surface silanols exposed at the quartz surface. Silanols (≡Si–OH) are known to behave in aqueous media as weak monoprotic Brønsted acid, exhibiting a dissociation constant that is dependent on the silanol structural arrangement with respect to neighbouring silanols (Hiemstra et al 1989 ; Bolis et al 1997 ; Pavan et al 2017 ). Silanols at silica surface can thus be described as families of silanols, sharing similar acidic properties that impart as a whole a specific surface charge (Pavan et al, under review/unpublished work).…”

Section: Resultsmentioning

confidence: 99%

“…The interaction of quartz particles with the phagolysosomal membrane, a crucial step according to the model of quartz-induced inflammogenicity, was recently proposed as the molecular initiating event (MIE) of the quartz adverse outcome pathway (AOP) towards persistent inflammation and silicosis (Pavan and Fubini 2017 ). In search for the molecular determinant of this interaction, a considerable number of works have been published in the last few years (Pavan et al 2013 , 2014 , 2017 ; Turci et al 2016 ; Joshi et al 2017 ). Traditionally, a well-established biomembrane model is represented by the red blood cell (Nolan et al 1981 ), and hemolysis is largely used to probe the interaction of amorphous and crystalline silica particles with biomembranes (Gerashchenko et al 2002 ; Zhao et al 2011 ; Pavan et al 2013 ).…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity of fractured quartz on THP-1 human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization

et al. 2020

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The pathogenicity of quartz involves lysosomal alteration in alveolar macrophages. This event triggers the inflammatory cascade that may lead to quartz-induced silicosis and eventually lung cancer. Experiments with synthetic quartz crystals recently showed that quartz dust is cytotoxic only when the atomic order of the crystal surfaces is upset by fracturing. Cytotoxicity was not observed when quartz had as-grown, unfractured surfaces. These findings raised questions on the potential impact of quartz surfaces on the phagolysosomal membrane upon internalization of the particles by macrophages. To gain insights on the surface-induced cytotoxicity of quartz, as-grown and fractured quartz particles in respirable size differing only in surface properties related to fracturing were prepared and physico-chemically characterized. Synthetic quartz particles were compared to a well-known toxic commercial quartz dust. Membranolysis was assessed on red blood cells, and quartz uptake, cell viability and effects on lysosomes were assessed on human PMA-differentiated THP-1 macrophages, upon exposing cells to increasing concentrations of quartz particles (10-250 µg/ml). All quartz samples were internalized, but only fractured quartz elicited cytotoxicity and phagolysosomal alterations. These effects were blunted when uptake was suppressed by incubating macrophages with particles at 4 °C. Membranolysis, but not cytotoxicity, was quenched when fractured quartz was incubated with cells in protein-supplemented medium. We propose that, upon internalization, the phagolysosome environment rapidly removes serum proteins from the quartz surface, restoring quartz membranolytic activity in the phagolysosomes. Our findings indicate that the cytotoxic activity of fractured quartz is elicited by promoting phagolysosomal membrane alteration.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity of fractured quartz on THP-1 human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization

et al. 2020

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“…The zeta potential of particles (ELS, measured in various medium at speci c pH), here used to describe the average acidity of surface silanols [29], acidic moieties with a potential for H-bonding, showed no signi cant differences among the set of samples, for the same medium. As expected, the zeta potential of particles dispersed in saline (0.01 M NaCl) at pH 4.5, which represents the lysosomal pH, was strongly negative (< -40 mV).…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity of fractured quartz on human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization.

Leinardi

Pavan

Yedavally

et al. 2020

Preprint

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Background The pathogenicity of quartz involves lysosomal alteration in alveolar macrophages. This event triggers the inflammatory cascade that may lead to quartz-induced silicosis and eventually lung cancer. Recently, we showed that synthetic quartz induces membrane lysis in red blood cells and cytotoxic responses in murine alveolar macrophages, only when the atomic order of crystal surfaces is upset by fracturing. Cytotoxicity was not observed when quartz exhibited as-grown, unfractured surfaces. These findings raised questions on the potential impact of quartz surfaces on the phagolysosomal membrane upon internalization of the particles by macrophages.Results To gain insights on the surface-induced cytotoxicity of quartz, as-grown and fractured quartz particles in respirable size, differing only in surface properties related to fracturing, were prepared and physico-chemically characterized. Their effects were compared to a well-known toxic commercial quartz dust. Membranolysis was assessed on red blood cells, and quartz uptake, cell viability, and impact on lysosomes were assessed on human PMA-differentiated THP-1 macrophages. All quartz samples were internalized, but only fractured quartz elicited cytotoxicity and phagolysosomal alterations. These effects were blunted when uptake was suppressed. Membranolysis, but not cytotoxicity, was quenched when fractured quartz surface was masked with serum proteins and incubated with cells.Conclusions Upon internalization, the phagolysosome environment rapidly removes serum proteins from quartz surface, restoring quartz membranolytic activity in the phagolysosomes. Fractured quartz induces cytotoxicity in THP-1 human macrophages by promoting phagolysosomal membrane alterations.

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“…1C), triggering ROS generation by mitochondria (6), activation of membrane NADPH oxidase complexes (7), and lysosome disruption leading to K + efflux and cathepsin B release. The physicochemical properties of the silica surface, namely the abundance, type, and extent of hydrogen bonding of surface silanols and ability to generate ROS, which depend upon processing pathway and environmental exposure, establish its hemolytic potential and cytotoxicity (8)(9)(10)(11). In PNAS, Pavan et al employ infrared spectroscopy and density functional theory to identify the structure of a unique subfamily of silanols (Fig.…”

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confidence: 99%

Are nearly free silanols a unifying structural determinant of silica particle toxicity?

Brinker

Butler

Garofalini

2020

Proc. Natl. Acad. Sci. U.S.A.

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Ζ potential evidences silanol heterogeneity induced by metal contaminants at the quartz surface: Implications in membrane damage

Cited by 17 publications

References 46 publications

Cytotoxicity of fractured quartz on THP-1 human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization

Cytotoxicity of fractured quartz on THP-1 human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization

Cytotoxicity of fractured quartz on human macrophages: role of the membranolytic activity of quartz and phagolysosome destabilization.

Are nearly free silanols a unifying structural determinant of silica particle toxicity?

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