California NanoSystems Institute

Joint Symposium on Nano-scale Research
into Biosenors, Biomaterials, and Nanotoxicology

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Bruce Dunn Department of Material Science and Engineering, UCLA	"Designing Bio-Hybrid Materials for Biosensor Applications" The flexible solution chemistry of the sol-gel process has been used to synthesize bio-hybrid materials in which a wide variety of biomolecules are encapsulated in a transparent, inorganic matrix. It is now well established that the dopant biomolecules retain their characteristic reactivities and spectroscopic properties despite being immobilized in the pores of the inorganic matrix. These materials have been widely explored as sensors with the biomolecule serving as both the biorecognition and transduction elements while the transparency of the matrix enables spectroscopic monitoring of the reactions. This paper reviews some of our recent work related to bio-hybrid based immunoassay approaches and the development of multi-functional materials.
Lei Jin Department of Microbiology, Immunology & Molecular Genetics, UCLA	"The atomic age for single-particle cryo-electron microscopy: 3.88Å cryoEM structure of cytoplasmic polyhedrosis virus" Elucidating the three-dimensional (3D) structures of biological systems plays a pivotal role in understanding molecular mechanisms in biology and medicine. For this purpose, there has been a long pursuit for generations of electron microscopists to "see", at atomic resolutions, the structures of biological nano-machines and macromolecular assemblies at their functional states. Recently we successfully pushed the resolution limit of single-particle cryoEM beyond 4Å using cytoplasmic polyhedrosis virus (CPV) as a model system. This is the highest-resolution structure ever achieved by this technology and has prompted ab initio atomic model building, a milestone toward atomic-resolution single-particle cryoEM. I will talk about our experience in this endeavor and the results of the 3D structure of CPV at 3.88Å resolution. With further advancement of cryoEM instrumentation, the development of more sophisticated algorithms and ever-growing computational power, there is every reason to believe that we are entering the age of atomic resolution for single-particle cryoEM, which will have profound impacts on biology, medicine and chemistry.
John Miao Department of Physics and Astronomy, UCLA	"Radiation Dose Reduction and Image Enhancement in Biological and Medical Imaging through Equally-Sloped Tomography"
Andre Nel CNSI, Division of NanoMedicine; Nanotoxicology; UCLA Medical Center	"Nanotoxicolgy as a Scientific Platform" Because of the large number of new nanomaterials that are being produced, it is of increasing importance to develop a platform for safety and risk assessment. It is probably not advisable to follow the example of chemical industry where the production of more than 80,000 industrial chemicals has overwhelmed toxicological screening capabilities. One of the principal stumbling blocks in assessing chemical toxicity has been the cost and the logistics to perform animal and in vivo studies. An intuitively more enlightened approach for nanotechnology would be to develop high throughput screening methods that incorporate a relevant toxicological injury mechanisms that can be related to the physicochemical properties of nanomaterials. I will discuss the emerging paradigms of toxicity that can be linked to the physicochemical properties of engineered nanoparticles with a view to outlining scientific principles that originate at the nano/bio interface and could determine whether interactions fail to occur, are biocompatible or injurious in nature. The major toxicological paradigm that have emerged from nanoparticle toxicity relates to the semiconductor, electronic, UV activation, and redox cycling chemistry of the particles, which allows them to induce tissue damage through the generation of oxygen radicals, electron-hole pairs and oxidant injury. It is possible to follow the oxygen radical generation and oxidant stress injury by abiotic methods as well as a set of hierarchical cellular responses that reflect protective, pro-inflammatory, mitochondrial damaging and pro-apoptotic outcomes. Another important paradigm relates to the ability of nanoparticles to absorb circulatory or cellular proteins as a function of particle size, surface area, functionalized surface groups, charge, hydrophobicity/hydrophilicity etc. This could induce protein unfolding, protein fibrillation, thiol crosslinking and loss of function, which could lead to neurotoxicity, loss of enzymatic activity, and generation of immunological responses. The thermodynamic properties and free surface energy of nanoparticles as a function of particle size, composition, phase and crystallinity could be responsible for particle dissolution in a biological environment, leading to the generation of cytotoxicity through the release of toxic ions or chemicals. Data are also emerging that indicate that cationic nanoparticles exert toxicity through the so-called proton sponge hypothesis, which postulates that particle uptake via acidifying endosomes leads to cellular toxicity through endosomal rupture, cytosolic deposition and mitochondrial targeting. The particle size, state of aggregation/dispersion, functional surface groups and hydrophobicity also plays an important role in determining the route of cellular uptake, subcellular localization and targeting of subcellular organelles. If used as a preliminary screen for newly emerging nanomaterials, these predictive science-based approaches can help to determine which materials should undergo priority testing in animal and in vivo exposure models.
Fuyu Tamanoi Department of Microbiology, Immunology & Molecular Genetics, UCLA	"Nanomachines for Targeted and On-Demand Release of Anticancer Drugs"
Shimon Weiss Department of Chemistry and Biochemistry, UCLA	"Single molecule probing of dynamic conformation, molecular interactions and dynamic localizations in-vitro, in live cells and in organisms" We applied single molecule spectroscopy using alternating laser excitation (ALEX) to the study of transcription initiation by e-coli RNA polymerase. We find that the transcription factor sigma70 is not obligatorily released in the transition from initiation to elongation and that the mechanism for abortive initiation is governed by DNA scrunching. We also applied ALEX spectroscopy to the study of protein folding. We find that the collapsed state of protein L is not driven by native contacts, and we show that Acyl-CoA binding protein (ACBP) has a residual structure in the denatured state. Lastly, we demonstrate the use of peptide-coated quantum dots for the study of lipid rafts in live cells' membranes and for molecular imaging in living cells and small organisms.