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

需要对生物膜和氧化硅（二氧化硅，SiO2）材料之间界面处的相互作用进行原子论理解，以合理化普遍存在且仅明显不同的现象，如二氧化硅生物矿化（或生物矿化）和二氧化硅纳米颗粒细胞毒性。我们提出了这样的假设，即特定的二氧化硅/膜识别模式，介导的水的分子结构在二氧化硅/水和膜/水界面，管理在磷脂双层的异相缩聚的油酸和溶血行为的某些类型的二氧化硅纳米粒子。该项目的目标是对磷脂膜模型和各种类型的二氧化硅之间的相互作用进行原子分子建模，范围从Si（OH）4分子缩合的早期产物到整个SiO2纳米颗粒。为了实现这一目标，我们的工作的第一个目标是现实模型的红细胞膜的建设，考虑到异质性和不对称的磷脂组合物在每两个膜小叶。这将与气相二氧化硅和胶体二氧化硅纳米粒子的真实模型的构建并行进行。这两种类型的二氧化硅的明显不同的界面结构、网络拓扑结构、孔隙率和水亲和力预期是其实质上不同的溶血和细胞毒性行为的关键。将通过先进的分子动力学技术（代谢动力学和溶质回火交换）研究尺寸不断增加的碳酸团聚体与膜模型的相互作用，目的是确定在团聚过程的哪个阶段（水合）二氧化硅在膜/水界面发生分离。最后，将在MD模拟中研究二氧化硅纳米粒子与膜模型的相互作用机制，以探索它们通过膜或粒子诱导的膜破裂的易位倾向。我们的研究结果所产生的知识，预计将提高我们的理解的机制，导致两个膜，整个细胞，甚至完整的生物体，以及溶血和细胞毒性的能力，但不是胶体无定形二氧化硅的烟雾。

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.