Study On Surface Modeling And Interaction Of Low Density Lipoprotein Affinity Film

Abnormally high level of plasma low-density lipoprotein (LDL) in human plasma is a key pathogenic factor that contributes to atherosclerosis and finally leads to coronary artery diseases (CAD). LDL-ahperesis has been of greatest concern for its high efficiency in removing LDL, especially during the treatment of patients with severeyperlipidemia. For over25years, a variety of LDL-reduction therapies have been established for clinical application, and a majority of researches have been concentrated on the adsorbents with excellent affinity to LDL. Therefore, the thesis is focused on the adsorption/desorption processes between LDL protein and surfaces modified with glycosyl and sulfonic groups to achieve an extremely high affinity to LDL. The main contents are listed below:Model surfaces were modified with different ratios of glycosyl to sulfonic group via mixed self-assembled monolayer (SAM) method, and the kinetics of the LDL adsorption processes with those mixed-SAMs were studied by surface plasmon resonance (SPR) technique. Results showed that the adsorbed amount of LDL on different modified model surfaces changed with the ratio of glycosyl to sulfonic groups, and had a maximum when it reached1.20. Therefore, the ’Multiple-Interaction Model’ was suggested to describe the synergism effect of the glycosyl group during the LDL adsorption process, which inferred the other interactions between glycosyl groups and LDL protein, beyond the electrostatistic interaction that had long been acquainted between sulfonic groups and LDL. Circular dichroism (CD) spectrum further affirmed the conclusion above by the detection of tertiary structure transformations of LDL protein when substances with glycosyl groups were added into.Therefore, according to the’ Multiple-Interaction Model’, the polysulfone (PSf) membranes were firstly UV irradiated and grafted with acrylic acid, then followed by the amidation and ’thiol-yne’ click modification to realize a glycosylation and sulfonation process, and finally to achieve the high affinity to LDL protein. The enzyme-linked immunosorbent assay (ELISA) was applied to investigate the adsorption and desorption process of those modified PSf membranes. Results suggested a maximum adsorbed amount of LDL as high as0.49μg/cm2, when the ratio of glycosyl to sulfonic groups of modified PSf membranes was found to be0.95. Meanwhile, the desorption efficiencies using NaC1/Urea (1:1) solution, of those membranes with both glycosyl and sulfonic groups, were higher than ones with single functional groups. All evidence above strongly supports that the ’Multiple-Interaction Model’can also be used for the membrane surfaces with complicated morphologies.This first-presented’Multiple-Interaction Model’should be helpful to the design and fabrication of new materials with high LDL affinity.