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）材料之间界面的相互作用进行原子性的理解，以使普遍存在的、只有明显不同的现象合理化，如二氧化硅生物矿化（或石化）和二氧化硅纳米颗粒细胞毒性。我们提出了一个假设，即特定的二氧化硅/膜识别模式，由二氧化硅/水和膜/水界面上的水分子结构介导，既控制了磷脂双层硅酸的非均相缩聚，也控制了某些类型二氧化硅纳米颗粒的溶血行为。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，我们工作的第一个目标是构建现实的红细胞膜模型，同时考虑到两个膜小叶中每一个膜中的不均匀和不对称磷脂组成。这将与气相和胶体二氧化硅纳米颗粒的现实模型的构建并行进行。这两种二氧化硅的界面结构、网络拓扑结构、孔隙率和亲水性明显不同，这被认为是它们溶血和细胞毒性显著不同的关键。通过先进的分子动力学技术（元动力学和溶质回火复制交换），将研究尺寸不断增大的硅酸团聚体与膜模型的相互作用，目的是确定团聚过程的哪个阶段在膜/水界面发生（水合）二氧化硅的分离。最后，将在MD模拟中研究二氧化硅纳米颗粒与膜模型的相互作用机制，以探索其通过膜的易位倾向或颗粒诱导的膜破裂。我们的结果所产生的知识有望提高我们对导致膜、整个细胞甚至完整生物体石化的机制的理解，以及对气相而非胶体无定形二氧化硅的溶血和细胞毒性的理解。

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.