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Foresight Update 6 (page 4)

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Table of Contents - Foresight Update 6

Recent Progress: Steps Toward Nanotechnology

by Russell Mills

Big projects

The Research Development Corporation of Japan is soliciting resumes from chemists and solid state physicists interested in researching the "architecture and function of self-assembling organic systems--their molecular design and synthesis, the introduction of function, and the creation of three-dimensional architecture." The 4-year effort is called the Kunitake Molecular Architecture Project, and is part of ERATO (Exploratory Research for Advanced Technology), sponsored by the Japanese Government. [Ad in Chem. & Eng. News: 18Jan88, p65]

Plans for the genome mapping project are coming into focus. The Program Advisory Committee on the Human Genome, formed by the National Institutes of Health to lead the project, has adopted a general strategy for the effort: [Science 243:167-168, 13Jan89]

Webmaster's Note: An abstract of the Kunitake Molecular Architecture Project, which ended in 1992, is available at:
A few of the many sources of information about The Human Genome Project available on the WWW:
Table of Contents - Foresight Update 6


Iwao Fujimasa at Tokyo University's Research Center for Advanced Science and Technology says his group is developing a robot small enough to travel inside the human body cutting and treating diseased parts in veins and organs. The goal is a machine less than .06 cm in size. [Wisconsin State Journal: 16Feb89]

Table of Contents - Foresight Update 6

Protein engineering

Proteins that have evolved by traditional means are not noted for their stability. They tend to unfold and become inactive when put into altered environments (like those likely to be encountered in commercial applications). But redesigning traditional proteins to make them more stable is feasible; a research group led by B. W. Matthews at the University of Oregon has provided a good example. Reasoning that helical segments of a protein chain might be stabilized by charged amino acids that interact with the dipole field of the helix itself, the group constructed several altered versions of the protein lysozyme from the phage T4 (which attacks the E. coli bacterium). Lysozyme, an enzyme that breaks up the cell wall of E. coli bacteria, contains 11 helical segments. The researchers used maps of the protein to select two of these helices for experimentation. They made three different lysozymes by substituting aspartic acid for an amino acid near an end of one or both of these helices. Measurements made on the resulting proteins revealed an increase in activity of 160% to 430%, and an increase in melting temperature of up to 4 degrees C. Since helical components are found in most active proteins, this method may be widely used to make proteins more resistant to temperature and other environmental conditions. [Nature 336:651-656, 15Dec88]

Other work done on T4 lysozyme by Matthews' group was aimed at incorporating a molecular "on-off switch" into the enzyme. In its native form, lysozyme has an open pit (or "active site") into which its substrate fits while being acted upon. The researchers designed a switch consisting of two thiol (-SH) groups. Under suitable chemical conditions, thiols can form covalent bridges with each other (-SS-); other conditions break the bridges (-SH HS-). A pair of thiols was built into lysozyme by replacing two amino acids on opposite sides of the enzyme's active site by cysteine--an amino acid with a thiol-containing side-chain. By changing the composition of the solution containing the experimental lysozyme, the researchers could cause the cysteines to form a bridge across the active site, completely inactivating the enzyme. The process was completely reversible. [Science 243:792-794, 10Feb89]

Biologists in Britain have successfully changed the preferred substrate of a bacterial enzyme. Lactate dehydrogenase (LDH) normally catalyzes the interconversion of pyruvate and lactate in the metabolism of sugars. Another enzyme, malate dehydrogenase (MDH) catalyzes an analogous interconversion of oxaloacetate and malate. Though structurally related, the amino acid sequences of the two enzymes are about 80% different. By making appropriate substitutions for 3 amino acids, the researchers turned LDH into a better catalyst for oxaloacetate/malate conversion than MDH itself. [Science 242:1541-1544, 16Dec88]

Many bacteria (including E. coli) propel themselves through water by rotating a helical filament called a flagellum. Flagella are driven at a few cycles per second by motors about 20 nanometers in diameter anchored in the bacterial membrane; power comes from a current of protons. Each motor is made of about 20 different polypeptides. Mutations in the genes for two of these proteins (MotA and MotB) result in bacteria with paralyzed flagella. When normal genes are then introduced into these bacteria, the paralysis is reversed--a turnover of MotA and MotB components in the flagellar motors seems to be a regular bacterial routine. At Harvard University videotapes have shown that the reversal of paralysis occurs as a series of 8 equal increases in torque. They conclude from this that there are eight torque generators in each flagellar motor.

Electron microscope images show rings of up to 16 particles in bacterial membranes of bacteria that produce MotA and MotB proteins. It therefore seems that a torque generator consists of two particles in which MotA and MotB occur.

The amino acid sequences of MotA and MotB proteins have led researchers to speculate that MotA contains a channel for conducting protons through the bacterial membrane, while MotB connects the torque-generating machinery to the membrane. [Science 242:1678-1681, 23Dec88]

Webmaster's Note: Pictures of the bacterial flagellar motor are available at:
Table of Contents - Foresight Update 6


As is well known, the scanning tunneling microscope (STM) can make images of conducting materials (metals, semiconductors) at atomic resolution. It has proved capable of imaging molecules of non-conducting materials, as well--a fact that has been difficult to explain, since the STM operates by passing an electron current between an electrode and the sample.

Researchers at IBM, Xerox, and Stanford University have now proposed a mechanism for this phenomenon. In the absence of a sample, a biasing voltage between an STM electrode and a graphite substrate allows a current to pass between electrode and substrate, overcoming an energy barrier in the process. But when a sample is adsorbed to the substrate, the size of the barrier is altered in the vicinity of the sample, thereby changing the rate of electron flow when the electrode passes over this region. The generality of this explanation suggests a much greater range of application for the STM than was originally thought. Researchers will be gleefully scanning all manner of materials for years to come. [Nature 338:137-139, 9Mar89]

A group at Berkeley, California has used an STM to study double-stranded DNA deposited onto graphite. The DNA was examined dry--in air rather than in solution--and was not given the conductive coating once thought to be necessary for electron tunneling to occur. The resolution achieved appeared to be finer than 1 nm; helical structure was clearly visible, as well as bumps that might correspond to individual DNA bases. [Science 243:370-372, 20Jan89]

[Suprisingly little is said in print about possible future use of STM images in the automated reading of genetic or amino-acid sequences.--RM]

Table of Contents - Foresight Update 6

Reliability and Performance

The reduction of thermal noise will likely be a major preoccupation of those who design nanomachines. The random jiggling of atoms in the components of such machines will reduce the accuracy of their intended motions, in some instances leading to lower performance or outright errors. These thermal motions can be reduced by cooling, but traditional methods of refrigeration become awkward and expensive when very low temperatures are needed.

Sophisticated cooling methods are now being suggested for microelectronic circuits, based on a concept called "stochastic cooling." In electronics applications, this would involve the detection of random current fluctuations and their cancellation by feedback. Electron temperatures under 10-6 K are in principle reachable by a stochastic refrigerator. [Nature 337:597-598, 16Feb89]

[The basic notion of stochastic cooling may be relevant to the problem of how to suppress the non-electronic thermal noise in nanomachinery, such as that which would interfere with the positioning of atoms by an assembler arm.--RM]

Dr. Mills has a degree in Biophysics and assists in the production of Update.

Table of Contents - Foresight Update 6

Foresight thanks Dave Kilbridge for converting Update 6 to html for this web page.

From Foresight Update 6, originally published 1 August 1989.
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