A nanoengineering approach towards the inhibition of the initial HIV infection

Organothiol self-assembled monolayers (SAMs) on Au(111) have been represented as model membrane systems. The first project addresses the structural information of aldehyde-terminated alkanethiol SAMs on Au(111) using scanning tunneling microscopy (STM) and atomic force microscopy (AFM). The structures of aldehyde-terminated alkanethiol SAMs are observed with molecular resolution. In comparison with alkanethiol SAMs, the aldehyde-termini SAMs have smaller domain sizes, lower degree of long-range order, larger coverage of disordered areas, and higher density of missing molecules and other point defects within domains of the closely packed molecules. The origin of these structural differences is mainly attributed to the strong dipole-dipole interactions among the aldehyde termini.Finally, the AFM based lithography and in situ characterization technique are used to investigate the geometry dependence of trimeric HIV-1 o-gp140DeltaV2 TV1 adsorption onto the designed 11-mercapto-1-undecanal (C10CHO) nanostructures. Our results indicate that (1) heavily glycosylated HIV-1 o-gp140DeltaV2 TV1 preferentially adsorbs on the 2D boundary edge of the engineered nanostructure regions compared to the pure C10CHO regions (2) nanoengineered structures exhibits a guiding effect for glycoprotein immobilization (3) the geometry dependence of gp140 immobilization on nanostructures, shows that the optimal ligand geometry for protein immobilization is 90° 16 x 16 crossed line (4) glycoprotein adsorption is stronger in crossed lines regions than in parallel line regions and the matrix, which indicated that the protein-CHO ligand interactions are polyvalent in nature (5) In situ AFM study are carried out in buffer solution, which proves that glycoproteins retain their integrity and bioactivity. The investigation demonstrates the potential of using engineered nanostructures for gp140 trimer immobilization, for applications requiring designed surface coverage.The second project utilizes a nanoengineering approach for the investigation and regulation of protein immobilization. It is known that protein attachment to surfaces depends upon the local structure and environment of the binding sites at the nanometer scale. Using nanografting and reversal nanografting techniques, protein binding sites with well-defined local environments are designed and engineered with nanometer precision. Three proteins, goat-anti-biotin Immunoglobulin G, lysozyme and rabbit-Immunoglobulin G, are immobilized onto these surfaces. Covalent attachment is achieved via primary amine residue on the protein and surface bound aldehyde-groups. Strong dependence on the dimension and spatial distribution of protein binding sites are revealed in antibody recognition.