Gang-yu Liu

Professor

Email: liu@chem.ucdavis.edu

Group Page

Nanoscience and Bioanalytical Chemistry

B.S., Peking University, P. R. China, 1985. M.A., Princeton University, 1987.
Ph.D., Princeton University, 1992.
CGP (Chemistry Graduate Program) Fellowship, Princeton University, 1986-1987.
Harold W. Dodds Honorific Fellowship, Princeton University, 1990-1991.
Miller Research Fellowship, University of California, Berkeley, 1992-1994.
Assistant Professor, Wayne State University, 1994-1999.
Camille and Henry Dreyfus New Faculty Award, 1994-1999.
Arnold and Mabel Beckman Young Investigator Award, 1996-1998.
Associate Professor with Tenure, Wayne State University, 1999.
Outstanding Scholarly Achievements Award, Wayne State University, 2000.
Career Development Chair Award, Wayne State University, 2000-2001.
Associate Professor with Tenure, UC Davis, 2001-2005
Professor, UC Davis, 2005.

Research Interests

Nanoscience and nanoengineering, bioanalytical chemistry, polyvalent biochemical interactions

Our overall research objective focuses on the development of nanotechnology and the application of nanotechnology in bioanalytical chemistry. One important aspect of the research is the designing and engineering nanostructures which position bioreceptors and chemical reaction sites on surfaces with high precision. The exquisite precision attainable by the nanolithographic methods that we have developed allows complex multivalent interactions typical of biorecognition to be controlled, by varying the separation and local environment of the binding sites. Students in the group acquire interdisciplinary training in start-of-the-art nanotechnology and are exposed to the forefront of nanoscience.

DEVELOPMENT OF NEW NANOFABRICATION TECHNIQUES

The research group has constructed state-of-the-art scanning tunneling microscopes and atomic force microscopes. True molecular resolution has been achieved for metal, semiconductor and organic thin film systems, and high resolution obtained for biological systems (e.g., DNA, proteins, viruses, and bacteria) using contact resonance imaging (CRI), a new imaging protocol developed in house.

Three atomic force microscopy (AFM) based nanofabrication techniques and two scanning tunneling microscopy (STM) based methods have been developed: nanoshaving, nanografting, nanopen reader and writer (NPRW), field-assisted diffusion and electron-induced evaporation. These nanofabrication methods are complementary. Among them, nanografting and NPRW are most frequently used for patterning SAMs. Compared with other nanofabrication techniques, nanografting has several unique advantages, as demonstrated in our research. First, a spatial resolution of 2 nm is routinely obtained for fabrication and molecular precision is likely to be achieved with a sharp tip. Second, nanostructures can be characterized in situ with molecular resolution, and their physical properties can be measured using the same tip. Third, once set up, one can quickly change the fabricated patterns in situ without changing the mask or repeating the entire fabrication procedure. Work is in progress to refine these techniques to further improve the resolution and throughput.

NEW CHEMICAL REACTION PATHWAY UNDER SPATIAL CONFINEMENT

The group believes that the chemical reaction mechanism and kinetics in a nanometer-confined environment may differ from the same reaction under unconstrained conditions. We have proven this hypothesis using surface reactions of self-assembly. Thiols that self-assemble onto gold surfaces in an unconstrained environment initially form a lying-down phase that subsequently goes through a phase transition to a standing-up phase. In contrast, under nanometer-confined conditions, e.g., during nanofabrication, thiol molecules bypass the lying-down intermediate and directly stand up, forming a highly ordered SAM. The resulting reaction kinetics is at least 100 times faster than the corresponding unconstrained reactions. Today, we and many other researchers are exploring new phenomena in the rapidly growing field of nanoscale science and engineering.

INVESTIGATION OF POLYVALENT ANTIBODY-ANTIGEN INTERACTIONS

Orientation and position specific immobilization of proteins on surfaces, such as antibodies, while maintaining their activity is a critical issue in the emerging field of nanobiotechnology. The development of methodology for such immobilization not only benefits the development of biotechnology, but also furthers our understanding of protein-membrane interactions, which are essential in the immune response to tumor cells, and to foreign antigens such as bacteria, viruses, allergens or toxins. Work is in progress to develop new methodologies to immobilize antibodies with designated positions while maintaining their bioreactivity. The perpendicular and lateral orientations of antibodies are also precisely controlled. The approach utilizes nanofabrication to produce nanostructures of ligands (antigens) followed by the divalent binding of antibodies with those nanostructures.

Specific procedures include the design and production of a series of nanostructures (or test platforms) in which the binding sites, i.e. antigens, are arranged with nanometer precision. Fabrication of nanostructures will be accomplished by using scanning probe microscopy-based lithographic techniques. The reaction of these test platforms with antibodies will be monitored using SPM in situ and in real time. Investigations of antibody-nanostructure interactions also provide information on reaction pathways and kinetics, the structure of the antibody-antigen complexes, and the binding strength and polyvalency. These nanostructures are specifically designed for: (1) systematic investigations of antibody-antigen interactions as a function of ligand separation, flexibility and local environment, from which the optimal designs for divalent immobilization are identified; (2) systematic comparisons of the nanoengineering approach of divalent protein immobilization, versus current methods which utilize mixed components or crystalline phase receptors.

The group is also developing methodology to produce assemblies of antibodies on surfaces, in which the relative position, and perpendicular and lateral orientations are precisely controlled. Finally, preliminary studies are proposed to test if these artificially engineered assemblies of antibodies can trigger cell responses, which mimic the corresponding immune processes, and how these responses differ from their natural counterparts.

IMMOBILIZATION OF BACTERIA VIA NANOFABRICATION AND POLYVALENT INTERACTIONS

Bacterial adhesion on surfaces is a critical initial step in their growth and infection processes. In addition, attaching bacteria on surfaces is also an important first step in sample collection for bacteria detection, especially for airborne bacteria during an outbreak in a natural environment or during hypothetical biowarfare. At present, airborne bacteria may be collected using cellulose-based membrane filters with micropores or channels. This method has the limitation of low selectivity, as other bacteria or microparticles are also collected, which could saturate the filter very rapidly. In collaboration with faculty members at NEAT, we plan to systematically investigate if the selectivity and saturation limit can be improved through chemical means, e.g. by using chemically modified and artificially engineered surfaces.

Publications

"Fabrication of Nanometer Scale Patterns within Self-Assembled Monolayers by Nanografting"
Xu, S.; Miller, S.; Laibinis, P. E.; Liu, G. Y. Langmuir 1999, 15, 7244-7251.

“Structural Basis of the Escherichia coli Outer-Membrane Permeability”
Amro, N. A.; Kotra, L. P.; Wadu-Mesthrige, K.; Bulchev, A.; Mobashery, S.; Liu, G.-Y. Proc. SPIE 1999, 3607, 108-122.

“Dynamics of the Lipopolysaccharide Assembly on the Surface of Escherichia coli”
Kotra, L. P.; Golemi, D.; Amro, N. A.; Liu, G.-Y.; Mobashery, S. J. Am. Chem. Soc. 1999, 121, 8707-8711.

“Fabrication and Imaging of Nanometer-Sized Protein Patterns”
Wadu-Mesthrige, K.; Xu, S.; Amro, N. A.; Liu, G.-Y. Langmuir 1999, 15, 8580-8583.

“Atomospheric Pressure Chemical Vapor Deposition of Titanium Aluminum Nitride Films”
Scheper, J. T.; Wadu-Mesthrige, K.; Proscia, J. W.; Liu, G.-Y.; Winter, C. H. Chem. Materials 1999, 11, 3490-3496.

“High-Resolution Atomic Force Microscopy Studies of the Escherichia Coli Outer Membrane: The Structural Basis for Permeability”
Amro, N. A.; Kotra, L. P.; Wadu-Mesthrige, K.; Bulchev, A.; Mobashery, S.; Liu, G.-Y. Langmuir 2000, 16(6), 2789-2796.

“Patterning Surface Using Tip Directed Displacement and Self-Assembly”
Amro, N. A.; Xu, S.; Liu, G.-Y. Langmuir 2000, 16(7), 3006-3009.

“Nanofabrication of Self-Assembled Monolayers Using Scanning Probe Lithography”
Liu, G.-Y.; Xu, S.; Qian, Y. Acc. Chem. Res. 2000, 33, 457-466.

“Arenethiols Form Ordered and Incommensurate Self-Assembled Monolayers on Au(111) Surfaces”
Yang, G.; Qian, Y.; Engtrakul, C.; Sita, L. R.; Liu, G.-Y. J. Phys. Chem B 2000, 104, 9059-9062.

“Nanomolar Scale Nitric Oxide Generation from Self-Assembled Monolayer Modified Gold Electrodes”
Hou, Y.; Chen, Y.; Amro, N.; Wadu-Mesthrige, K.; Andreana, P. R.; Liu, G. Y.; Wang, P. G. Chem. Commun. 2000, 19, 1831-1832.

“Visualizing Bacteria at High Resolution”
Kotra, L. P.; Amro, N. A.; Liu, G. Y.; Mobashery, S. ASM News 2000, 66, 675-681.

“Immobilization of Proteins on Self-assembled Monolayers”
Wadu-Mesthrige, K.; Amro, N. A.; Liu, G.-Y. Scanning 2000, 22, 380-388.

“Nanocomposites by Electrostatic Interactions”
Auer, F.; Scotti, M.; Ulman, A.; Jordan, R.; Sellergren, B.; Garno, J.; Liu, G.-Y. Langmuir, 2000, 16, 7554-7557.

“Polytetrahydrofuran Cross-Linked Polystyrene Resins for Solid-Phase Organic Synthesis:”
Toy, P. H.; Reger, T. S.; Garibay, P.; Garno, J. C.; Malikeyil, J. A.; Liu, G.-Y.; Janda, K. D. J. Combinatorial Chem. 2001, 3, 117-124.

“Fabrication of Nanometer-Sized Protein Patterns Using Atomic Force Microscopy and Selective Immobilization”
Wadu-Mesthrige, K.; Amro, N. A.; Garno, J. C.; Liu, G. Y. Biophysical J. 2001, 80, 1891-1899.

“Nanofabrication Using Computer-Assisted Design and Automated Vector-Scanning Probe Lithography”
Cruchon-Dupeyrat, S.; Porthun, S.; Liu, G. Y. Applied Surface Science 2001, 175-176, 636-642.

“Characterization of AFM Tips Using Nanografting”
Xu, S.; Amro, N.; Liu, G.-Y. Applied Surface Science 2001, 175-176, 649-655.

“Contact Resonance Imaging — A Simple Approach to Improve the Resolution of AFM for Biological and Polymeric Materials”
Wadu-Mesthrige, K.; Amro, N. A.; Garno, J. C.; Liu, G. Y. Applied Surface Science 2001, 175-176, 391-398.

“Self-assembled rigid monolayers of 4 '-substituted-4- mercaptobiphenyls on gold and silver surfaces”
Kang, J. F.; Ulman, A.; Liao, S.; Jordan, R.; Yang, G. H.; Liu, G. Y. Langmuir 2001, 17, 95-106.

“Room Temperature Solution Synthesis of Alkyl-Capped Tetrahedral Shaped Silicon Nanocrystals”
Baldwin, R. K.; Pettigrew, K. A.; Garno, J. C.; Power, P. P.; Liu, G. Y.; Kauzlarich, S. M. J. Am. Chem. Soc. 2002, 124(7), 1150-1151.

“Positioning Proteins on Surfaces: A Nanoengineering Approach to Supramolecular Chemistry”
Liu, G. Y.; Amro, N. A. PNAS 2002, 99, 5165-5170.

“Production of Nanostructures of DNA on Surfaces”
Liu, M.; Amro, N. A.; Chow, C. S. Nano Letters 2002, 2(8), 863-867.

“Self-assembled multilayers of 4,4 '-dimercaptobiphenyl formed by Cu(II)-catalyzed oxidation”
Brower, T. L.; Garno, J. C.; Ulman, A.; Liu, G. Y.; Yan, C.; Golzhauser, A.; Grunze, M. Langmuir 2002, 18, 6207-6216.

“Three-Dimensional Nanostructure Construction via Nanografting: Positive and Negative Pattern Transfer”
Liu, J.; Cruchon-Dupeyrat, S.; Frommer, J.; Liu, G. Y. Nano Letters 2002, 2(9), 937-940.

“Production of Periodic Arrays of Protein Nanostructures”
Garno, J. C.; Amro, N. A.; Wadu-Mesthrige, K.; Liu, G. Y. Langmuir 2002, 18, 8186-8192.

“Nanostructures of Organic Molecules and Proteins on Surfaces”
Amro, N. A.; Garno, J. C.; Liu, M.; Wadu-Mesthrige, K.; Liu, G.-Y. Proc. SPIE 2002, 4807, 10-22.

“Precise Positioning of Nanoparticles on Surfaces Using Scanning Probe Lithography”
Garno, J. C.; Yang, Y.; Amro, N. A.; Cruchon-Dupeyrat, S.; Chen, S.; Liu, G. Y. Nano Letters 2003, 3, 389-395.

“Structures of Annealed Decanethiol SAMs on Gold: an UHV-STM Study”
Qian, Y.; Yang, G. H.; Jung, T.; Liu, G. Y. Langmuir 2003, 19, 6056-6065.

“New Insights for Self-Assembled Monolayers of Organothiols Revealed by Scanning Tunneling Microscopy”
Yang, G.; Liu, G. Y. J. Phys. Chem. Feature Article, 2003, 107, 8746-8759.

“Synthesis of gold glyconanoparticles and biological evaluation of recombinant Gp120 interactions”
Nolting, B.; Yu, J. J.; Liu, G. Y.; Cho, S. J.; Kauzlarich, S.; Gervay-Hague, J. Langmuir 2003, 19, 6465-6473.

“Scanning probe lithography of self-assembled monolayers”
Yang, G.; Amro, N. A.; Liu, G.-Y. Proc. SPIE 2003, 5220, 52-65.

“Molecular Level Approach to Inhibit Degradations of Alkanethiol Self-assembled Monolayers in Aqueous Media”
Yang, G.; Amro, N. A.; Starkewolfe, Z. B.; Liu, G. Y. Langmuir 2003, 20, 3995-4003.

“Hybridization with Nanostructures of Single-Stranded DNA”
Liu, M.; Liu, G. Y. Langmuir 2005, 21, 1972-1978.

“Single Electron Tunneling and Manipulation of Nanoparticles on Surfaces at Room Temperature”
Yang, G.; Tan, L.; Yang, Y.; Chen, S.; Liu, G. Y. Surf. Sci. 2005, 589, 129-138.

“Probing Local Structure and Mechanical Response of Using Force Modulation and Nanofabrication”
Price, W. J.; Kuo, P. K.; Lee, T. R.; Colorado R.; Ying, Z. C.; Liu, G. Y. Langmuir 2005, 21, 8422-8428.

“Polyvalent Interactions of HIV-gp120 Protein and Nanostructures of Carbohydrate Ligands”
Yu, J.; Nolting, B.; Tan, Y. H.; Li, X.; Gervay-Hague, J.; Liu, G. Y. Nanobiotechnology 2006, 1, 201-210.

“Measuring the Size Dependence of Young’s Modulus Using Force Modulation Atomic Force Microscopy”
Price, W. J.; Leigh, S. A.; Hsu, S. M.; Patten, T. E.; Liu, G. Y. J. Phys. Chem. 2006, 110, 1382-1388.

“A Simple Miniaturization Protocol to Produce Multi-component Micro- and Nano-structures”
Ouyang, Z.; Tan, L.; Liu, M.; Judge, O. S.; Zhang, X.; Li, H.; Hu, J.; Patten, T. E.; Liu, G. Y. SMALL 2006, 7, 884-887 (cover).

“Cell Mechanics Using Atomic Force Microscopy Based Single Cell Compression”
Lulevich, V.; Zink, T.; Chen, H.; Liu, F.; Liu, G. Y. Langmuir 2006, 22(19), 8151-8155 (cover).

“A Nanoengineering Approach to Regulate the Lateral Heterogeneity of Self-Assembled Monolayers”
Yu, J.; Tan, Y. H.; Li, X.; Kuo, P. K.; Liu, G. Y. J. Am. Chem. Soc. 2006, 128(35), 11574-11581.

“High-Efficiency Stepwise Contraction and Adsorption Nanolithography”
Tan, L.; Ouyang, Z.; Liu, M.; Ell, J.; Hu, J.; Patten, T. E.; Liu, G.-Y. J. Phys. Chem. B 2006, 110(46), 23315-23320.

“Significance of Local Density of States in the Scanning Tunneling Microscopy Imaging of Alkanethiol Self-assembled Monolayers”
Riposan, A.; Liu, G.-Y. J. Phys. Chem. B 2006, 110(47), 23926-23937.