Molecular recognition between membrane epitopes and nearly free surface silanols on silica: a new paradigm for particle toxicity mechanism
- 1Department of Chemistry, University of Turin, Italy
- 2G. Scansetti Research Center on Asbestos and Other Toxic Particulates, University of Turin, Italy (centroscansetti@unito.it)
- 3Louvain centre for Toxicology and Applied Pharmacology, Université catholique de Louvain, Bruxelles, Belgium
- 4Center for Environmental Health Sciences, Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, United States of America
Respirable crystalline silica (RCS) is the leading cause of occupational respiratory disease worldwide. RCS is associated with silicosis, cancer, and autoimmune diseases [1]. Silica (SiO2) is a simple, yet structurally very complex oxide and tens of variable crystalline and amorphous forms exist with different structures and surfaces. Structural heterogeneity is reflected in variable toxic effects, and this in turn generates one of the most intriguing enigmas in particle toxicology, i.e., deciphering the exact molecular nature of the interaction between silica and biological matter.
A large set of synthetic and natural, crystalline and amorphous, micrometric and nanometric silica particles were prepared, modified, and characterized. The interaction of these surface-modified silicas with membrane systems of decreasing molecular complexity, e.g., red blood cells, liposomes, and phospholipid supramolecular structures (PLS), was investigated and compared with the results of in vitro and in vivo particle toxicity assessment.
A specific silanol (≡Si-OH) sub-group at silica surface, the “nearly free silanols” (NFS), was evidenced as the cause for the membranolytic and inflammatory effect of silica [2]. Silica powders with NFS-rich surfaces caused RBC membrane lysis, and selectively perturbed liposomes and adsorbed PLS. Specific amino groups exposed at the membrane surface are proposed as recognition epitopes for the selective interaction with NFS, which are in turn proposed as the molecular pattern that defines the interaction of silica with biomembranes [3]. Our findings open a new perspective for tailoring less toxic silica particles and for designing improved technological applications of silica. NFS and hydroxylated surface moieties may be also relevant for the toxicity of other respirable mineral dusts, suggesting a new paradigm for particle toxicity mechanism.
References
[1] Leung et al., Lancet 2012, 379, 2008; [2] Pavan et al., Proc. Natl. Acad. Sci USA 2020, 117, 27836; [3] Pavan et al., sumbitted to ACS Central Science
How to cite: Turci, F., Pavan, C., Bellomo, C., Cananà, S., Rebba, E., Sydor, M., Leinardi, R., Kendall, R., Mino, L., Holian, A., and Lison, D.: Molecular recognition between membrane epitopes and nearly free surface silanols on silica: a new paradigm for particle toxicity mechanism, EGU General Assembly 2022, Vienna, Austria, 23–27 May 2022, EGU22-10497, https://doi.org/10.5194/egusphere-egu22-10497, 2022.
