Nearly free silanols drive the interaction of crystalline silica polymorphs with membranes: Implications for mineral toxicity

Abstract

Crystalline silica (CS) is a well-known hazardous material that causes severe diseases including silicosis, lung cancer, and autoimmune diseases. However, the hazard associated to crystalline silica is extremely variable and depends on some specific characteristics, including crystal structure and surface chemistry. The crystalline silica polymorphs share the SiO2 stoichiometry and differentiate for crystal structure. The different crystal lattices in turn expose differently ordered hydroxyl groups at the crystal surface, i.e., the silanols. The nearly free silanols (NFS), a specific population of weakly interacting silanols, have been recently advanced as the key surface feature that governs recognition mechanisms between quartz and cell membrane, initiating toxicity. We showed here that the nearly free silanols occur on the other crystalline silica polymorphs and take part in the molecular interactions with biomembranes. A set of crystalline silica polymorphs, including quartz, cristobalite, tridymite, coesite, and stishovite, was physico-chemically characterized and the membranolytic activity was assessed using red blood cells as model membranes. Infrared spectroscopy in highly controlled conditions was used to profile the surface silanol topochemistry and the occurrence of surface nearly free silanols on crystalline silica polymorphs. All crystalline silica polymorphs, but stishovite were membranolytic. Notably, pristine stishovite did not exhibited surface nearly free silanols. The topochemistry of surface silanols was modulated by thermal treatments, and we showed that the occurrence of nearly free silanols paralleled the membranolytic activity for the crystalline silica polymorphs. These results provide a comprehensive understanding of the structure-activity relationship between nearly free silanols and membranolytic activity of crystalline silica polymorphs, offering a possible clue for interpreting the molecular mechanisms associated with silica hazard and bio-minero-chemical interfacial phenomena, including prebiotic chemistry.

Physico-Chemical Approaches to Investigate Surface Hydroxyls as Determinants of Molecular Initiating Events in Oxide Particle Toxicity

“…These characteristics are commonly found in crystalline silica polymorphs, specifically quartz and cristobalite. The methodology to properly process IR data to obtain information on the OH population on these kinds of samples has recently been presented by our group [1,45,46]. In addition, assuming that the accuracy of the measurements is not affected by instrumental errors but depends only on the difference in reflectance, it is possible to estimate the relative error associated with the Kubelka-Munk function by deriving the function F(R∞) with respect to R∞.…”

“…These characteristics are commonly found in crystalline silica polymorphs, specifically quartz and cristobalite. The methodology to properly process IR data to obtain information on the OH population on these kinds of samples has recently been presented by our group [1,45,46].…”

“…Mechanistically, NFS-rich but not NFS-poor silicas were proven to induce cytotoxicity in macrophages, leading to the secretion of alarmin IL-1α as one of the early inflammatory events triggered by silica particles [43]. A positive correlation between the presence of surface NFS and the membranolytic capacity of silica was proven for synthetic and natural quartz, amorphous silica [1,44], crystalline silica polymorphs [45], and crystalline nanosilica prepared by ball milling [46]. Overall, recent research evidenced that NFS are a solid candidate to explain the different biological effects of many types and structures of silica specimens.…”

“…The selected range 2800-2300 cm −1 shows νOD patterns of surface silanols for the two samples. Adapted with permission from[26,45].…”