Molecular Dynamics simulations of the interaction between silica and phospholipid membranes in the context of biomineralization and nanotoxicity

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An atomistic understanding of the interactions at the interfaces between biological membranes and silicon oxide (silica, SiO2) materials is required to rationalize ubiquitous and only apparently diverse phenomena such as silica biomineralization (or fossilization) and silica nanoparticle cytotoxicity. We put forward the hypothesis that specific silica/membrane recognition patterns, mediated by the molecular structure of water at the silica/water and membrane/water interfaces, govern both the heterogeneous polycondensation of silicic acid at phospholipid bilayers and the haemolytic behaviour of certain types of silica nanoparticles. The goal of this project is to perform atomistic molecular modeling of the interactions between phospholipid membrane models and various type of silica, ranging from the early products of the condensation of Si(OH)4 molecules up to whole SiO2 nanoparticles. To achieve this aim, a first objective of our work is the construction of realistic models of red blood cell membranes taking into account the heterogeneous and asymmetric phospholipid composition in each of the two membrane leaflets. This will proceed in parallel to the construction of realistic models of both fumed and colloidal silica nanoparticles. The markedly different interfacial structure, network topology, porosity and water affinity of these two types of silica are expected to be the key for their substantially different haemolytic and cytotoxic behaviours. The interaction of silicic acid agglomerates of increasing size with membrane models will be studied by means of advanced Molecular Dynamics techniques (Metadynamics and Replica Exchange with Solute Tempering) with the objective of determining at which stage of the agglomeration process does a segregation of (hydrated) silica take place at the membrane/water interface. Finally, the interaction mechanisms of silica nanoparticles with membrane models will be studied in MD simulations in order to explore their propensity for translocation through the membrane or the particle-induced membrane rupture. The knowledge generated by our results is expected to improve our understanding of the mechanisms leading both to the fossilization of membranes, entire cells or even complete organisms, and to the hemolytic and cytotoxic power of fumed but not colloidal amorphous silica.