DNA molecules

Scientists track the influence of a cancer inhibitor on a single DNA molecule

Researchers in Delft University of Technology’s Kavli Institute of Nanoscience in The Netherlands have cast new light on the workings of the important cancer inhibitor topotecan. Little had been known about the underlying molecular mechanism, but the Delft scientists can now view the effects of the medicine live at the levelin of a single DNA molecule.

The research is being published this week in the journal Nature. The lead author of the article, Daniel Koster, will receive his PhD at TU Delft on Monday June 25, partly on the results described in the article.

The medicine investigated, topotecan, interacts with an important protein (TopoIB), causing a (cancer) cell to malfunction. The TopoIB protein is responsible for the removal of loops from DNA, which arise amongst other things during cell division. The TopoIB protein binds to the DNA molecule, clamps around it and cuts one of the two DNA strands, after which it allows it to unwind and finally joins the broken ends together. PhD candidate Daniel Koster, Master’s student Elisa Bot and researcher Nynke Dekker of the Molecular Biophysics group of the Kavli Institute of Nanoscience Delft have managed to unravel this mechanism in an extremely direct manner. In the laboratory they fixed a single DNA molecule between a glass plate and a magnetic sphere. With the help of two magnets they could both pull and twist the DNA molecule. When they added TopoIB to a twisted piece of DNA, they saw that the loops were slowly removed.

What is exceptional is that the action of one TopoIB enzyme on one DNA molecule could be observed live. In collaboration with St. Jude Children’s Research Hospital Memphis (USA) the mechanism could also be observed in living yeast cells.

New nano-method

A team of chemists at Brown University have devised a simple way to synthesize iron-platinum nanorods and nanowires while controlling both size and composition. Nanorods with uniform shape and magnetic alignment are one key to the next generation of high-density information storage, but have been difficult to make in bulk.

[Simply changing the ratio of two chemicals in solution changes the length of iron-platinum nanowires and nanorods: transmission electron microscope images of a) 200 nm wires; b) 50 nm wires; c) 20 nm rods; d) two individual 50 nm wires. Credit: Chao Wang & Jaemin Kim/Brown University]

The technique, published online June 22 in the journal Angewandte Chemie International Edition, pro-duces nanorods and nanowires from 20 nm to 200 nm long, simply by varying the ratio of sol-vent and surfactant used in synthesis. Shouheng Sun, a professor of chemistry at Brown Univer-sity, postdoctoral researcher Yanglong Hou, and colleagues have also demonstrated that the same technique works to control the shape of cobalt-platinum nanorods, suggesting that it may work for many other combinations as well.

Just a few years ago, the average computer user’s documents, applications and even photos seemed to rattle around a 120 GB disk drive. Today’s multimedia-intensive user can exhaust that capacity in no time and the need continues to grow, but engineers expect to max out conven-tional magnetic storage techniques by about 2010. At that point, they’ll be looking for nanotech-nology to step up.

Whether it will be ready, remains to be seen. Getting tiny magnetic particles to align with each other has been one of the major obstacles to squeezing more information density out of the technology. Sun and Hou think they can harness particle shape to accomplish that critical task. “Many people think that shape can control alignment,” said Sun, “but controlling shape has not been so easy. This method gives us a really simple way to tune length, diameter and composition all at the same time.” A magnetic storage surface – the disk of a hard-disk drive -- consists of tiny sectors of magneti-cally-aligned particles. When the read-write head of a disk drive passes over a sector, it flips the magnetic field to the opposite direction – encoding a zero or a one. When it reads, it senses the magnetic field for the whole sector.

To pack more information into a smaller area, engineers can make the particles smaller or the sectors smaller, but they need enough particles so that the occa-sional random flip doesn’t corrupt the whole sector. It is now possible to apply magnetic nanoparticles in a thin, dense layer, but the magnetic fields of randomly-oriented spherical particles tend to cancel each other out. Instead of lining up at six o’clock or twelve o’clock, many particles align at two, three, four or five o’clock, diluting the overall strength of the magnetic signal.

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