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

Abstract

The interaction of silica (SiO 2 ) 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 SiO 2 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.

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“…It should be noted that the membrane before inserting DDS well equilibrated for 20 ns (Figure S4) which can be confirmed by computing the area per lipid. The area per lipid for the membrane is around of 52.24 Å 2 /lipid which has a good agreement with reported similar membranes (53.0 Å 2 /lipid) 46 …”

Structural basis for high selectivity of a rice silicon channel Lsi1

“…The MD simulation was based on the CHARMM force field for protein residues 40 and lipids 45 . For Si(OH) 4 , we employed the parameter set reported by Piane et al 46 , except for the parameter set for the O−H bond, which was taken from the generalized Amber force field (GAFF) 47 . The atomic partial charges of Si(OH) 4 were determined by fitting the electrostatic potential by using the RESP procedure 48 .…”

The puzzling issue of silica toxicity: are silanols bridging the gaps between surface states and pathogenicity?

“…So-called ‘enhanced’ sampling methods have been introduced to alleviate this problem [60], and have reached enough maturity to be used for investigation of the complex interface between silica and the biological world. Recent results on the effects of silica nanoclusters of various size and features on membrane models of different composition shed light on the determinants of particle toxicity [12]. Simulations provided a first atomistic picture of the interactions taking place between silica and the membrane of cells, gaining a quantification of the energetics of this process, depending on silica cluster size, membrane composition and cholesterol content.…”