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Careers in Nanobiotechnology: Biomolecular Machines


The miniaturisation of electrical components may be causing a revolution in the electronics industry, but some scientists have their sights set on things much smaller than silicon chips. Nanotechnology is a rapidly expanding field that is starting to produce new devices that will transform the way we live. However, nature has already spent millennia developing its own machines, and it is to these preexisting materials that physicists and engineers are turning.

Nanotechnology is the construction of machines and devices on the nanometer scale--that is a millionth of a millimetre. At this scale the machines are constructed from individual atoms and, according to Ralph Merkle from Zyvex, "It really does matter how atoms are arranged." As he points out, a computer chip is only rearranged sand with a few impurities thrown in. Nanotechnology became a reality when it became possible to hold atoms still and assemble them in an organised manner. James Gimzewski from IBM in Zurich says that the scanning tunnelling microscopes (STM) that first allowed researchers to look at individual atoms "became an extension of the human experience." More recently, atomic force microscopes have allowed atoms to be picked up and put down again, and STMs now have the power to snip off bits of molecules by cleaving chemical bonds.

Back in 1959, physicist Richard Feynman suggested that physicists look at biological systems to see how nature stores information and builds nanoscale structures. Indeed, nanotechnology has now turned to biology to understand how synthetic machines work and to examine those that nature has developed over time. As Richard Palmer, head of the Nanoscale Physics Research Laboratory at the University of Birmingham, puts it, "Atoms don't know if they are in a physics, chemistry, or biology lab ... [the] boundaries between science die away." Even biotechnology companies are encouraging the interdisciplinary approach--Novartis has a 12-year plan to extensively develop nanotechnology in the life sciences.

Proteins are nature's machines and their three-dimensional shape determines their function. Over the last 3 decades researchers have been determining the structures of a variety of proteins at an exponential rate. Some of these proteins have been motors, pumps, or signalling machines. There are many different biomolecular motors in the cell, including those responsible for muscle or cell movement. Their fuel is a chemical called adenosine triphosphate, or ATP. An example is ATP synthase, which has two rotary motors, Fo and F1. In this remarkable molecule the F1 motor uses the energy from ATP to drive the Fo motor to pump protons across a membrane, or alternatively, the proton-driven Fo motor drives the F1 motor to create ATP. Molecular motors have entire conferences dedicated to them, involving both biologists and physicists and showing the increasingly interdisciplinary nature of nanotechnology. Such collaborations are bearing fruit; 18 months ago scientists from Boston College in Massachusetts published their synthesis of a 78-atom motor in Nature that uses chemical energy in a manner reminiscent of ATP to power its ratchetlike movement. However, as it takes several hours to make one revolution, there is still some way to go.

Replication is another area of biology that nanotechnologists are interested in. According to Merkle, they want their devices to self-replicate so that they can make them "inexpensively, in large quantities." The replicating molecule in nature is DNA, and its many copies are essential for cellular control and the continuation of life. Nanotechnologists, however, are quick to remind us that "self-replication doesn't mean living." In fact, they are looking at systems that replicate quite differently from biological material.

Nanotechnology is producing results. One aim is to link the molecular motion from a nanomotor to a much larger scale motion, just like linking the motion of individual proteins to a muscle contraction. In a separate project, Gimzewski is trying to develop a molecular valve system based on DNA. His group has built a system where two different lengths of DNA bind together to cause a cantilever bend. Their aim is to sense the bending motion and convert this into a signal that causes a valve to open and close. In another application, nanostructured surfaces could be used to arrange biomolecules. Palmer believes that they could build a template that would bind virus or protein molecules. This could increase the number of protein structures known, as one method of structure determination involves crystallising the protein. Many proteins fail to form crystals, but forcing them into a regular pattern on a nanosurface might overcome this problem.

Another promising area of nanotechnology is nanomedicine. Merkle says that our current surgical tools are huge in comparison to our needs at the molecular level. He predicts that nanomedicine would allow us to tackle medical problems directly--nanomachines could tackle cancer cells and bacteria directly and could remove circulatory obstructions. Nanotechnology could even make artificial red blood cells.

Despite the fact that manufacturing technology has become more diverse, more precise and cheaper, Merkle still thinks it will be a matter of some years before the first nanotechnology devices are available. However, he also believes that "there is a huge range of possibilities which we have not even started to touch." Palmer agrees: "For me it's an exciting frontier in science."