Molecular Dynamics Simulations of the Silica-Cell Membrane Interaction: Insights on Biomineralization and Nanotoxicity

The interaction of silica (SiO2) with biological systems is complex and contradictory. On the one hand, silica is at the basis of several biomineralization processes (e.g., in sponges). On the other hand, silica nanoparticles and dust may lead to silicosis and, at the cellular level, hemolysis. These toxic responses are strongly dependent on the silica polymorph and their root causes are still under debate. Both silica biomineralization and silica-induced nanotoxicity could be related to similar mechanisms of molecular recognition between the cellular membranes and the surface of the SiO2 particles. On the basis of this hypothesis, we employed classical molecular dynamics simulations, coupled to advanced sampling techniques, to achieve an atomistic picture of the interactions between different types of silica nanoparticles and the membrane of erythrocytes. Our predicted free-energy profiles associated with membrane crossing give no evidence for segregation of nanoparticles at the membrane/water interface, irrespective of their Si nuclearity, structure, and charge. The associated molecular trajectories, however, are suggestive of a possible direct translocation mechanism, in which silica nanoclusters elicit both local and large-scale effects on the membrane dynamics and stability. This gives hints on possible pathways for silica nanotoxicity based on nanoparticle-induced membrane perforation.