Researchers at Caltech, JPL, and Univ. São Paulo, Brazil have designed
(but not built) a molecular-sized shift register--a memory storage device
with 1000 times the density and a ten-thousandth the energy consumption
of its VLSI equivalent. Bits are stored by bumping individual electrons
into the energy levels of a polymer, where they are moved along the polymer
as more bits are written. The design has been worked out in some detail,
and specifies the orbital energy levels of the molecules, the rates of competing
(error-producing) electron transitions, spacing of the polymers, and the
timing of the read/write cycle. The authors state that the register and
associated read/write devices could be implemented with current technology;
they provide chemical formulas of candidate molecules. [Science
241:817-820 (12Aug88)]
Molecular-sized conducting wires of lengths down to 3 nanometers have been
made at the Univ. of Minnesota from polyacenequinone and imide subunits.
The researchers hope to generate 3-D networks under 10 nm in size using
similar chemical techniques. [New Scientist (19May88)] Webmaster's Note: More current information
about molecular electronics and molecular wires can be found on the WWW,
for example:
Herschel Rabitz
at Princeton Univ. proposes using femtosecond laser pulses to excite molecules
in solution, measuring their response, and using the data to craft another
pulse--thus homing in on the pulse structure needed to produce a desired
chemical reaction. Once the correct pulse structure is known, it could be
used routinely to carry out the reaction while dispensing with the elaborate
techniques now required to protect one part of the molecule while another
part is being modified. If Rabitz's method works, it may shorten many of
the paths to nanotechnology by drastically simplifying the assembly of complicated
molecules. [Science News 134:6 (2Jul88)] Webmaster's
Note: A recent bibliography of information on ultrafast lasers
is available on the WWW at:
A technique has been developed at Bell Labs for trapping and manipulating
microorganisms without damaging them. A lens is used to focus a laser on
the organism; light refraction results in a force that pushes it toward
the focal point of the beam. Viruses and bacteria can be trapped and immobilized
by the technique; larger cells, such as yeast or protozoa, can be dragged
around by moving the beam. The investigators even found that they could
reach inside a cell with the laser beam, grasp internal organelles and move
them around. One wonders whether a similar technique could be used to assemble
components of micromachines like those discussed elsewhere in this article.
[Science 241:1042 (26Aug88)]
Physicists at the National Bureau of Standards are now able to confine groups
of sodium atoms between a set of laser beams and then slow down their motions
to under 20 cm/sec. Under these conditions the properties of atoms can be
studied with very high precision; such information will someday be needed
for the design of nanomachines and zero-tolerance materials. [Science
241:1041-1042 (26Aug88)]
A step forward in our ability to handle individual molecules has been made
by Japanese researchers at Osaka Univ. who have directly measured the tensile
strength of an intermolecular bond--by pulling on it until it broke. The
bond is that between protein subunits in a skeletal muscle filament. The
filaments are chains of "actin" molecules held together by non-covalent
bonds; two such chains wind around each another to form an actin filament.
Another protein, "myosin", contains the motor apparatus of the
muscle. The researchers obtained a value of 108 piconewtons for the tensile
strength of actin filaments. They proceeded to measure the force exerted
by each myosin "motor" as it pulls on an actin filament--about
1 pN. Since each actin filament is pulled on by roughly 50 myosin molecules,
there would seem to be a safety factor of 2 built into our muscles. [Nature
334:74-76 (Jul88)] Webmaster's Note: For more current information
on:
using optical techniques to manipulate cells, sub-cellular components, and
other micrometer-scale objects:
Biochemists at Cornell Univ. are now able to take 120 picosecond x-ray diffraction
exposures of organic molecules and enzymes. This breakthrough is made possible
by a magnetic "undulator" that produces an intense x-ray beam.
Until now, x-ray diffraction analysis has required long exposures, especially
for large molecules. Molecular motion would cause the images to blur, thus
limiting the resolution obtained. With exposure times now reduced by a million-fold,
it should be possible to watch enzymes change shape as they catalyze reactions
and to troubleshoot nanomachines by observing them in action. [Science
241:295 (15Jul88)]
An electric motor less than half a millimeter across, miniature air-driven
turbines, and gear trains--these are among the various micromachines recently
fabricated at the Univ. of Calif. at Berkeley, Cornell Univ., and Bell Labs
using the techniques of integrated circuit manufacture. Intended to provide
measurements of friction, wear, viscosity, lubrication, stress, deformation,
fatigue and other factors at the scale of microtechnology, they may be forerunners
of practical devices: tiny fans for cooling integrated circuits, drug-dispensing
mechanisms for smart pills, cutting tools for unblocking blood vessels,
cell sorters for diagnostic tests. Similar methods might be used to make
even smaller machines, but true nanomachines are probably beyond the range
of these techniques. [Science 242:379-380 (21Oct88)]
Webmaster's Note: A few of the many WWW pages
with micromachinery information:
Victim of numerous court-ordered delays inspired by unfounded fears, the
U.S. biotechnology industry has finally realized that it can no longer take
public awareness for granted. Some companies have dealt with the problem
by hiring public relations firms to promote positive attitudes toward them;
often this approach has led to company-sponsored public meetings in communities
where the testing of genetically modified organisms is being planned. The
effectiveness of the effort is already evident--more than a dozen field
tests have been conducted recently without controversy. [Science
242:503-505 (28Oct88)] Nanotechnology proponents: take note! Technophobia
is an easy nut to crack when moderate resources are devoted to the effort.
Wm.
DeGrado's group at the duPont Co. has continued to make remarkable progress
in protein design and production. Having designed a four-helix protein that
self-assembles into a stable bundle, they proceeded to synthesize the gene
for this protein, insert the gene into a bacterium, and show that the bacterium
produces the desired protein. Although this effort aimed at studying the
relationship between amino-acid sequence and 3-dimensional structure of
proteins, the designed protein will probably be used as a "platform"
for adding functional features. [Science 241:976-978
(19Aug88)]
The molecules responsible for photon-capture in photosynthesis were mapped
in detail several years ago. To find out how they work, scientists at MIT
and Washington Univ. (St. Louis) are making amino-acid substitutions in
the reaction center of photosynthetic bacteria. When they altered an important
amino acid linking a chlorophyll molecule with its protein support, one
of the chlorophyll subunits lost its magnesium atom--yet the system still
functioned at about 50% efficiency. This suggests that photosynthesis does
not depend critically on the molecular structures arrived at through traditional
evolution, and that better and simpler molecules may be developed for powering
some kinds of nanomachinery. [Science News 134:292]
Biological membranes are equipped with a variety of channels connecting
the inside and outside of cells or organelles. These channels, made of protein,
can be opened and closed; when open they allow certain ions to pass through
the cell membrane. Wm. DeGrado's group at duPont has designed and synthesized
a number of simple ion channel proteins and tested their ability to form
functional ion channels in a phospholipid membrane. The proteins were chains
of 14 to 21 serine and leucine residues, arranged into helical structures
with the polar serines running down one side and the apolar leucines along
the opposite side. A number of these helices would then aggregate in parallel
to form a cylindrical bundle around a central channel. The researchers determined
that 21-residue proteins spanned the membrane and created a conductive path
for ions. The amino-acid sequence of the proteins determined the number
of helices in a bundle, and this in turn determined the size of ions that
could pass through the channel. [Science 240:1177-1181
(27May88)] More on artificial ion channels: http://www.scripps.edu/pub/ghadiri/html/nature94.htm Protein engineering advances swiftly. In each of the following three
summaries, researchers have programmed Escherichia coli bacteria
to produce and secrete redesigned antibody molecules. Bacteria are far easier
to program and grow than eukaryotic (nucleated) cells, but in earlier experiments
bacteria would not output functional proteins. In the latest work the bacteria
have been persuaded to produce "antigen-binding fragments" (Fabs)
with the same specificity and affinity for their substrates as the original
antibodies.
Researchers at Max Planck Institute developed a bacterial expression system
mimicking the one eukaryotes use. In eukaryotic cells, an antibody's protein
chains are synthesized in the cell's cytoplasm, then transported into an
organelle called the "endoplasmic reticulum," where they are trimmed,
folded, bonded, and paired into a functioning configuration. The researchers
first examined the 3-dimensional structure of the antibody MCPC603 and decided
which portions of it to keep. They next constructed a custom plasmid (mini-chromosome)
consisting of: the DNA sequences coding for the antigen-binding portions
of the antibody's protein chains, two bacterial "signal sequences"
coding for protein appendages that tell the bacterial cell membrane to secrete
the proteins, and several other sequences required for replication and translation
of the DNA via RNA into protein. When this plasmid was introduced into Escherichia
coli, the bacteria used the new DNA to make and secrete the Fab protein
chains. The chains then folded and bonded themselves correctly. [Science
240:1038-1041 (20May88)]
A group at International Genetic Engineering, Inc. used essentially the
same technique to produce a chimeric Fab consisting of antigen recognition
domains taken from a mouse antibody, and the remainder taken from human
antibody (presumably to forestall an immune attack on the Fab if it should
be used therapeutically in humans). This particular Fab was chosen because
it attacks human colon cancer cells. [Science 240:1041-1043
(20May88)]
Genex Corp. researchers have gone a step further in simplifying antibody
molecules. Traditional antibodies are composed of four polypeptide chains.
In the Genex design, two of these chains are eliminated and the other two
are joined by a short chain of amino acids. The result is called a "single-chain
antigen-binding protein." Genes to encode several such proteins were
constructed and expressed in E. coli. The proteins produced by the
bacterium proved to have the same specificity and affinity for the substrates
as the original antibodies. Single-chain antigen-binding proteins are expected
to replace monoclonal antibodies in such areas as cancer and cardiovascular
therapy, assays, separations, and biosensors. [Science 242:423-426
(21Oct88)]
Amidases are enzymes that catalyze the hydrolysis of amide bonds. Of particular
interest to biotechnologists are amidases specific for the amide bonds connecting
amino acids together in proteins; what is needed are tools for cutting a
protein at any desired place along its amino acid sequence. Researchers
at Scripps Clinic and Penn State Univ. have overcome a major hurdle by developing
a Fab that catalyzes the hydrolysis of a somewhat different amide bond joining
two aryl components. Mice were immunized with a compound resembling the
transition state of amide hydrolysis; whole antibodies collected from the
mice were then enzymatically trimmed. The resulting Fabs sped up the hydrolysis
reaction by a factor of 250,000. [Science 241:1188-1191
(2Sep88)]
Dr. Mills has a degree in Biophysics and assists in the production of
Update.
