19 Jul, 2007 10:59 am
At the nanoscale - the order of billionths of a meter, materials exhibit unique optical, electronic, and magnetic properties not seen at the bulk scale. The combination of these unique properties with proteins and macromolecules found throughout cells and their biological components has motivated the introduction of nanoparticles as labels and probes for incorporation into biological systems.
Biofuels, as a new energy resource, are expected to reduce greenhouse gas emissions and other pollutants, and revitalize the economy by increasing demand and prices for agricultural products. Scientists have been searching for efficient ways to convert organic fuels such as ethanol into electricity. Some biological molecules can oxidize ethanol to generate free electrons, and directly produce electricity, using gold nanoparticles as a conductive path (2). One obstacle to producing an efficient enzyme electrode is to coat the electrode with the enzymes in a densely-packed layer. Here, we have taken bacterial enzyme complexes and shown by electron microscopy that an oriented and ordered monolayers could be assembled in solutions using functionalized gold nanoparticles to “glue” the enzymes together. These monolayers are mechanically stable enough to be transferred onto solid surfaces. This newly developed nanotechnology provides a solution to create “bio-electrodes” coated with densely packed redox enzyme, which could lead to more efficient energy conversion devices from biomass.
The human body contains thousands of different proteins, which play essential roles in maintaining life. A protein's structure determines the specific role that protein plays in the human body; however, researchers lack detailed knowledge about the structures of many proteins, many of which are directly related to diseases. low-temperature freeze-Sample electron microscopy is an emerging technique to determine the three-dimensional structure of a protein, and further understand the dynamics of molecular machines. Although the rapid freezing of a protein solution enables its structural studies under its physiological environment, the low electron exposure necessary for minimizing radiation damage gives noisy recorded images. Our approach to assembling nanoparticle-protein arrays could facilitate the detection of low-contrast protein molecules, and improve the precision of image alignment and classification that are required for boosting signal level. This method might enable analysis of small biological macromolecules and complexes which are currently largely intractable by low-temperature freeze-Sample electron microscopy single particle analysis. Although we only tested two proteins in our experiments, the method is flexible in that binding sites can be programmed by genetic engineering at various sites of the biomolecule, and the size of gold nanoparticles can be adjusted to make array architectures match protein binding geometries. Therefore, a two-dimensional crystal could be formed without complicated crystallization processes, which could enable determination of biological macromolecules to higher structural resolution.
Our method to control the geometry of nanoparticle-protein binding complexes is important for detection, characterization, and therapy of diseases. Tunable surface chemistry further facilitates the coating, functionalization, and integration of nanoparticles with a host of biomolecular groups. We found that smaller gold nanoparticles can only bind to one protein molecule, whereas larger ones can bind to several protein molecules. The presented method could be used to join nanoparticles with antibodies targeted to receptors overexpressed on cancer cells, for example. The nanoparticles can also carry drugs. Importantly, they themselves can be used as hyperthermia therapy, i.e., use of optical heating for killing tumors, or to increase tumor x-ray absorption during radiotherapy for more effective treatment of cancer. By employing appropriate targeting strategies, the imaging/therapy scheme can be made generic to a variety of cancers and even extended to other diseases.
1) Minghui Hu, et al. Assembly of nanoparticle-protein binding complexes: from monomers to ordered arrays, Angewandte Chemie International Edition (2007) 46: 5111-5114.
2) Yi Xiao, et al. Plugging into enzymes: nanowiring of redox enzymes by a gold nanoparticle. Science (2003) 299: 1877-1881.