Dynamic Behaviors Of Protein On Heterogeneous Surfaces

Almost all the surfaces in nature exhibit non-uniformity,that is,heterogeneous surfaces.According to the chemical and physical properties of the surface,heterogeneous surface can be divided into zwitterionic heterogeneity,amphiphilic heterogeneity and topographic heterogeneity.For example,the cell membrane is a typical heterogeneous interface consisting of zwitterionic,amphiphilic,and a rough heterogeneous structure.Studies have shown that the neat phospholipid bilayer can repel proteins,but cell membranes contain not only phospholipids but also glycans and membrane proteins.Glycans at cell interfaces play a key role in molecular recognition and can specifically bind to incoming proteins to determine the final biological processes.Moreover,the design of biomaterials not only requires the use of heterogeneous surfaces to diagnose and treat diseases,replace damaged organs and improve the functions of certain tissues,but also needs to avoid the side effects of the adhesion and growth of human proteins or cells.Therefore,the study of the interactions between proteins and heterogeneous interfaces not only plays an important role in better understanding biological phenomena and life processes,but also provides a theoretical basis for the design and preparation of biological functional materials.The main research contents of this thesis consist of the following two parts:(1)Non-specific interactions between proteins and polymeric heterogeneous surfaces.Biomaterials typically use nanostructured surfaces to control the interactions between protein and the surfaces,thus regulate their biological functions.How do polymer nanostructure surfaces repel or adhere to proteins? Its molecular mechanisms and design rules are still lacking,this greatly restricts the development of highperformance biomaterials through the rational design of nanostructures.We investigated the dynamic behaviors of different size protein molecules on the surface of polymer nanostructures with different adhesive domain.Using Surface Plasmon Resonance and Single-molecule-tracking techniques,we reveal that the 2D diffusion behaviors of protein molecules on the surface is the decisive factor for protein resistance on the surface of nanostructures.The adhesive domain must be more than ten or hundreds of times of the footprint size of the protein,to slow down the twodimensional diffusivity of the protein,and then adsorption occurs.We established a physical model for quantitative analysis of the kinetics of surface repel or adhere to proteins in nanostructures.Our method is universal and can be applied to all kinds of heterogeneous surfaces,such as amphiphilic,low surface energy and charged heterogeneous surface materials.(2)Polyvalent specific interactions between influenza virus hemagglutinin HA protein and the glycan interfaces.The polyvalent interaction between proteins and glycan molecules on the cytomembrane interface is a key physical process of virus infection with the human body.Current studies qualitatively describe the process of virus invasion into cells,quantitatively analyze the mechanism of the interaction between virus and cell membrane are still lacking,because the proteins on the surface of the virus exist almost as oligomers rather than as individual protein molecules,which greatly limits our understanding of the process of viral infection and the design and preparation of effective antiviral drugs.In order to solve this problem,we used the single particle tracking technique to track the adhesion process of influenza virus hemagglutinin HA model nanoparticles at the glycolipid membranes in real time,with surface glycan density varying over 4 orders of magnitude.By quantitatively analyzing the Langmuir adhesion equation of HA and glycosolipid,The HA/glycan monovalent and polyvalent specific binding processes were distinguished at the low and high glycan densities,in addition,the quantity level of the multivalent combination process is given.Based on the new model,we also successfully quantitatively analyzed the multivalent interactions between antiviral drugs and virus model particles,which provided important theoretical significance for the design and preparation of effective antiviral drugs.