Theoretical Investigation On Interfacial Modification And Size Effect Of Gold Nanoclusters Interacting With Cell Membranes

Due to the excellent stability,biocompatibility and tunability,the Aunanomaterials exhibit potential applications in the areas of biosensor,drug delivery,and antimicrobial,in which the size and interfacial modification of Au nanomaterials are the key issues.Considering that the interaction process between clusters and cell membrane is an important step in the application behavior,this thesis choose thiolate-protected gold nanoclusters（RS-AuNCs）with well-defined chemical composition and topological structure as a model.The interaction processes between cell membrane and gold nanoclusters with different sizes,different stacking patterns,and different interfacial modifications have been studied through molecular dynamics,based upon which the microcosmic mechanism of interaction between Aunanocluster and membrane is further concluded from the atomic scale.In order to accurately describe RS-AuNCs with different sizes and different stacking patterns in the force field,this thesis refers to the adjacency matrix describing undirected topological graphs in graph theory,and establishes a connectivity database describing the cluster topology and atom type.The atoms were divided into different types based on connectivity,radial distance and atomic charge,followed by fitting their parameters,and summarizing a universal force field containing forcefield parameters of diverse atom types.The research contents of this thesis are as follows:1、We selected the widely used Au₂₅（SR）₁₈^-as the cluster model,and investigated the effect of mercaptohexanoic acid（MHA）,p-mercaptobenzoic acid（MBA）ligands and cysteine（Cys）ligands on the cluster-cell membrane interaction process.Different systems showed the similar energy trend,that is,the spontaneous migration trend from the water phase to the cell membrane surface and the monotonous increasing trend of migration from the cell membrane surface to the cell membrane centroid.Under the circumstance of modification with a single type of ligand,Au₂₅-MBA induced the highest topological deformation on both hydrophilic head group and hydrophobic tail chain of the cell membrane.Therefore,the energy barrier（74.7 kcal/mol）that the Au₂₅cluster with MBA ligand needs to overcome is higher than that of MHA（66.4kcal/mol）and Cys（64.2 kcal/mol）ligand.As for 12MHA-6MBA and 15MHA-3MBA cluster system,despite the fact that MBA has highest energy barrier in case of single ligand modification,the energy barrier of Au₂₅-12MHA-6MBA（66.5 kcal/mol）with a higher MBA ratio was lower than that of Au₂₅-15MHA-3MBA（79.2 kcal/mol）.This phenomenon is believed to originate from the more regular distribution of ligands in 12MHA-6MBA,leading to higher symmetry of the entire cluster.As for a cluster possessing the same topology,size and type of ligand as Au₂₅cluster,the transmembrane energy barrier range of Ag₂₅（SR）₁₈^-clusters is 104.3-108.5 kcal/mol,which is higher compared with for Au₂₅（SR）₁₈^-.The above studies show that the type of ligand,the spatial arrangement of the ligand,and the type of metal atoms all affect the process of the cluster entering the cell membrane.2、We discussed the interaction process between the cluster series with regular structure evolution and the cell membrane,and summarized the related microscopic interaction rules by focusing on the internal relationship between the evolution behavior of the cluster structure and the microscopic interaction rules.We selected two different growth patterns of face-centered cubic（fcc）series clusters with MHA ligands:Au₂₈（SR）₂₀-Au₃₆（SR）₂₄-Au₄₄（SR）₂₈-Au₅₂（SR）₃₂,Au₂₂（SR）₁₈-Au₂₈（SR）₂₀-Au₃₄（SR）₂₂-Au₄₀（SR）₂₄.The energy barriers of the Au₂₈（SR）₂₀-Au₃₆（SR）₂₄-Au₄₄（SR）₂₈-Au₅₂（SR）₃₂during transmembrane process are 57.04,83.8,89.8 and 108.6 kcal/mol respectively,exhibiting an increasing trend along with the increase of the cluster size.The energy barriers of Au₂₂（SR）₁₈-Au₂₈（SR）₂₀-Au₃₄（SR）₂₂-Au₄₀（SR）₂₄series clusters were46.6,45.4,43.3 and 78.3 kcal/mol,showing an initial decreasing and following increasing trend.In particular,the discrepancy between Au₂₈（SR）₂₀（45.4 kcal/mol）with toroidal tetrahedral core and Au₂₈（SR）₂₀（57.04kcal/mol）of the double-helix chain tetrahedral core emphasizes the influence of topological structure.In addition,we also explored the free energy changes of the non-fcc-packed clusters Au₃₈（SR）₂₄and Au₁₀₂（SR）₄₄during the transmembrane process,which were 65.8 kcal/mol and 146.6 kcal/mol,respectively.The above studies show that the size,packing mode and topological structural of the clusters are the key factors affecting the transmembrane process of the clusters.In this thesis,the effects of ligand specie,spatial arrangement,metal atom species and size on the transmembrane process were explored from a microscopic perspective,providing theoretical guidance for the development of multifunctional gold nanomaterials.