Book Review: Biological Molecules in Nanotechnology
Biological Molecules in Nanotechnology: The Convergence of Biotechnology, Polymer Chemistry and Materials Science
Editors: Stephen C. Lee and Lynn M. Savage
International Business Communications, Inc. (1998)
Adapted from the IBC conference "Biological Approaches and Novel Applications for Molecular Nanotechnology," held December 8-9, 1997, in La Jolla, CA, USA.
Softcover; 183 pages. ISBN 1-57936-109-9
Reviewed by James B. Lewis, Ph.D.
The book and the conference from which it developed address nanobiological devices, defined by the editor as "...devices in which nanoscale synthetic components were used to organize the functional biological macromolecules that performed the work of the device..." The articles in this volume present the argument that (1) "technology for building nanomachines with functional biological components is here today," and (2) "no 'fatal flaw' has yet been identified for the nanobiological approach to nanotechnology." The first ten chapters deal with enabling technologies for nanobiological devices, and the last six with current applications of biologic nanotechnology.
Commenting in detail on individual chapters is beyond the scope of this brief review, but taken together the contributions in this book provide a good overview of the state of nanobiological devices as of 1997. The focus is remote from molecular manufacturing, that is, developing technology to build a wide range of complex structures and devices to atomic precision. Instead, various approaches are presented to link biomolecules in Rube Goldberg fashion to a scaffolding of synthetic nanometer-scale molecular materials to improve the function of these molecules for applications in biotechnology and as novel materials. Such devices are usually not built to atomic precision, although critical components are defined to atomic precision, and the structures are uniform in size to within a few nm or less.
One chapter explores starburst PAMAM (polyamidoamine) dendrimers, more or less spherical particles, ranging from 1.5 to 14 nm in diameter, built up by successive cycles of linking together branched organic molecules. These particles are only approximately defined molecularly (due to incomplete reaction as the particles become larger), but they provide a rich array of sites that can be chemically functionalized to produce specialized particles for a variety of biotechnology applications, such as drug delivery.
Another class of spherical particles of 10-100 nm diameter is the topic of a chapter on stabilized micellar structures. Termed shell crosslinked knedel-like nanospheres, they are built by the self-assembly of block copolymers, linear molecules in which one half is hydrophobic and the other half is hydrophilic. Self association of like halves results in a sphere with a hydrophobic interior and a hydrophilic shell. Judicious choice of chemical substituents on the polymer permits covalent crosslinking of the shell to make the spheres more robust than were they held together only by the non-covalent bonds that drive self assembly. As with the dendrimers, many chemical variations are available to tailor dimensions, core and shell thickness, chemical reactivity, etc. to fit a wide variety of applications from drug delivery to novel materials.
A chapter on carbon nanotubes proposes ways in which mechanical stress directly applied to the nanotube could be used to direct chemical reactions to specific regions of the nanotube.
An example in which the nanobiological device is built to atomic precision is the chapter on using DNA for technological purposes that are unrelated to its biological role as the genetic material. This novel use of the unique molecular recognition properties of DNA strands has enabled substantial progress toward several goals: constructing "crystalline scaffolds to solve the macromolecular crystallization problem, to create new memory devices, and to facilitate nanofabrication"; controlling DNA folding topology to generate self-replicating objects and new materials; assembling nanomechanical devices. Another chapter explores use of electric fields to position DNA molecules on 20 to 80 micron patches on semiconductor chips, and to use the molecular recognition properties of DNA to self assemble photonic and electronic devices by linking the components to appropriate DNA sequences.
The challenge of adapting protein molecules evolved to function in a specific biological environment to functioning in very different environments in nanobiological devices is the topic of several chapters. Specific examples of success in such re-engineering are not presented, but the wide array of techniques used successfully in biotechnology to provide proteins for specific purposes is summarized to argue that such re-engineering should be feasible. Further, the ability to chemically ligate together short polypeptides synthesized using organic chemistry, which can include non-biological amino acids and other molecules that the ribosome can not use, broadens the range of possibilities far beyond the kinds of proteins found in nature. Linking biomolecules to dendrimers opens other avenues to constructing nanobiological devices.
The applications discussed include MEMS technology to make micro-pumps crucial to cm-sized "lab-on-a-chip" devices, molecular separations achieved by membranes containing nanotubules formed by depositing gold in the pores of the membranes, and surface patterns formed using crystalline bacterial cell surface layers (S-layers).
The latter are especially interesting because a range of protein species provides a 2- to 8-nm range of pore sizes, with each species giving a molecularly precise ultrafilitration membrane. The uniform orientation of the proteins furthermore provides a uniform array of reactive groups that can be chemically functionalized. Also being developed is a 3-D (volumetric) optical memory in which the molecular switch is bacteriorhodopsin, a bacterial photosynthetic protein. Another group is using scanning electrochemical microscopy to develop very sensitive probes for specific biomolecules on single cells. A final chapter surveys problems with medical applications of nanobiological devices, citing as examples failures in separate gene transfer attempts using adenoviruses and dendrimers due to severe, unexpected side effects.
The contributors are prominent researchers, and they provide brief authoritative overviews of their fields, but the papers are too short to be comprehensive reviews. The book totals 183 pages, with several black and white illustrations and one or two dozen references per paper. Although the book provides a readable and informative overview of its subject, it is necessarily dated since much relevant research has been accomplished since the book was published. Thus the price quoted on the IBC website (http://www.ibcusa.com) and in brochures seems unreasonably expensive - $895 for commercial purchase and $195 for purchasers with verifiable academic status.
Jim Lewis holds a Ph.D. in Chemistry (Harvard University, 1972), and has held positions as a Senior Research Investigator with Bristol-Myers Squibb Pharmaceutical Research Institute and an associate member Associate Member, Basic Sciences Division, Fred Hutchinson Cancer Research Center (both in Seattle). He currently consults on technologies leading to molecular manufacturing and nanotechnology, and also serves as the Webmaster for the Foresight Institute.
A Foresight Profile:
University of Washington Center for NanoTechnology
The Center for NanoTechnology (CNT), at the University of Washington in Seattle, was established in 1997.The Center was created with $1 million from Washington State's University Initiatives Fund, which reallocates resources from throughout the university to underwrite innovative new programs strategically selected to strengthen the University and seize opportunities that otherwise would not be pursued.
The Director of the CNT is Dr. Viola Vogel, Associate Professor in the Department of Bioengineering and Adjunct Professor of Physics, who presented on her work with natural molecular motor systems at the Sixth Foresight Conference in November 1998.
"Nano-scale science and technology is about to come of age," Vogel said in January 1998, shortly after the CNT was established. "If the University really wants to be on the cutting edge we have to be big in nanotechnology. The goal of this center is to create a vibrant intellectual and educational hub for the University that cuts across department and college boundaries so that the state of Washington can help lead this technological revolution."
Dr. Charles T. Campbell, Professor, Department of Chemistry and Adjunct Professor of Physics, is Co-Director. Also speaking in 1998, Campbell said, "It is widely recognized throughout the research community, both in academia and industry, that the next century will be dominated by developments in nanotechnology just as the past quarter of a century has been dominated by microtechnology."
The CNT coordinates an interdisciplinary approach to research and education in nano-scale science and engineering. Over three dozen faculty members from the University's Schools of Arts & Sciences, Medicine, Engineering, and Pharmacy in such diverse fields as Chemistry, Physics, Biophysics and Bioengineering, Chemical Engineering, Electrical Engineering, Materials Science & Engineering, and Molecular Biotechnology are affiliated with the CNT, providing a broad, interdisciplinary base.
In addition to their own research, the faculty associated with the CNT offer a range of courses and seminars, broadly grouped under:
Properties of Materials at the Nanoscale
Nanoengineered Particles and Materials
Microfabrication & Nanofabrication
Functional Protein Complexes
Plans for the CNT program include development of an interdisciplinary minor in nanotechnology, designed and taught by faculty from various departments and open to students from throughout the University.
A centralized NanoTech User Facility (NUF) is equipped with two state-of-the-art Scanning Probe Microscopes: a Digital Multimode Nanoscope and a TopoMetrix Explorer combined with a Leica inverted optical microscope. It also houses an Environmental Scanning Electron Microscope. NUF is available to UW, other academic, research, and industrial users as a cost center.
The UW nanotechnology center's has a strong focus on biochemistry and biotechnology that is unique in the country, according to Vogel and Campbell. The University's international reputation for excellence in biomedical sciences and engineering, coupled with the burgeoning local biotechnology industry, positions the Puget Sound region as the national leader in biomedical applications of nanotechnology, they maintain.