4. Cooperative assembly of nanoscopic objects with biomolecules.

 

Nanotechnology is expected to lead the next industrial revolution. Engineered nanomaterials are increasingly applied in various fields, such as catalysis, composite materials, cosmetics, microelectronics, drug delivery and medical diagnostics. Although their beneficial outcome is infinite, the possible toxic health effects of these nanomaterials, when exposed to human, raised a lot of concerns recently [1-4]. For instance, inhalation of the carcinogenic nanoparticles has long been suspected as the cause of lung cancer [5]. The interactions of nanoscopic objects with biomolecules control their metabolic pathways that are key for their desired functions as well as inherent toxicity, but are poorly understood.

 

When the dimensions of nanoscopic objects reach that of biomolecules, cooperative assembly between them is expected. Since most important biomolecules such as lipids, proteins and nucleic acids are charged in aqueous solution, so do many waterborne nanoscopic objects coming in contact with living systems, electrostatics ought to play an important role to define their assembly behavior. Complex assemblies driven by “wet electronics” are abundant in biological systems. Examples include chromatin in cell nucleus consisting of hierarchically wrapped DNA chains around nanoscopic histone octamers [6], DNA torus condensed by polyvalent cations in bacteriophages [7], and many others [8,9]. We are interested in studying the cooperative assembly of synthetic nanoscopic objects with biomolecules, with an emphasis on how electrostatics defines their assembly behavior.

 

As a prototypical system, interactions of biomolecules with waterborne nano-golds that have well-controllable sizes and charge distributions are investigated. The gold quantumdots have tunable sizes ranging from 2-3 times the diameter of a hydrated ion to the size of a globular protein. Gold nanodrods on the other hand, resemble 1-D objects such as DNA, cytoskeleton filaments, and many viruses.

nanogold

 

Nano-golds not only serve as ideal models to study the electrostatic interactions in nanoscale that have significant biological relevance, but also represent different classes of nanomedicine currently under development [10]. Examples include dendimers for drug delivery and imaging agents, quantum dots for imaging and diagnostics, fullerenes for drug delivery and therapeutics, nanoshells and nanotubes for tumor ablation, and so forth. Studying the size- and charge-dependent interactions of nano-gold with biomolecules provides a window to understand the in vivo fates of nanoscopic objects coming in contact with living system. It also points new avenues to organize nanoscopic objects bio-mimetically into functional devices [11-13]. Nature has done a beautiful job to hierarchically assemble different building blocks-many of them are of nanoscale-into macroscopically functional units. Much remains to be learnt to rationally assemble nanomaterials at different length scales.

[1] Gwinn, M. R.; Vallyathan, V. Nanoparticles: Health effects - Pros and cons. Environmental Health Perspectives 2006, 114, 1818-1825.

[2] Donaldson, K.; Aitken, R.; Tran, L.; Stone, V.; Duffin, R.; Forrest, G.; Alexander, A. Carbon nanotubes: A review of their properties in relation to pulmonary toxicology and workplace safety. Toxicological Sciences 2006, 92, 5-22.

[3] Nel, A.; Xia, T.; Madler, L.; Li, N. Toxic potential of materials at the nanolevel. Science 2006, 311, 622-627.

[4] Oberdorster, G.; Oberdorster, E.; Oberdorster, J. Nanotoxicology: An emerging discipline evolving from studies of ultrafine particles. Environmental Health Perspectives 2005, 113, 823-839.

[5] Donaldson, K.; Stone, V.; Tran, C. L.; Kreyling, W.; Borm, P. J. A. Nanotoxicology. Occupational and Environmental Medicine 2004, 61, 727-728.

[6] Akey, C. W.; Luger, K. Histone chaperones and nucleosome assembly. Current Opinion in Structural Biology 2003, 13, 6-14.

[7] Gelbart, W. M.; Bruinsma, R. F.; Pincus, P. A.; Parsegian, V. A. DNA-inspired electrostatics. Physics Today 2000, 53, 38-44.

[8] Honig, B.; Nicholls, A. Classical Electrostatics in Biology and Chemistry. Science 1995, 268, 1144-1149.

[9] Levy, Y.; Onuchic, J. N. Mechanisms of protein assembly: Lessons from minimalist models. Accounts of Chemical Research 2006, 39, 135-142.

[10] Dobrovolskaia, M. A.; McNeil, S. E. Immunological properties of engineered nanomaterials. Nature Nanotechnology 2007, 2, 469-478.

[11] Scheffel, A.; Gruska, M.; Faivre, D.; Linaroudis, A.; Plitzko, J. M.; Schuler, D. An acidic protein aligns magnetosomes along a filamentous structure in magnetotactic bacteria. Nature 2006, 440, 110-114.

[12] Sarikaya, M.; Tamerler, C.; Jen, A. K. Y.; Schulten, K.; Baneyx, F. Molecular biomimetics: nanotechnology through biology. Nature Materials 2003, 2, 577-585.

[13] Zhang, S. G. Fabrication of novel biomaterials through molecular self-assembly. Nature Biotechnology 2003, 21, 1171-1178.