Heavy equipment is needed to get molecules into formation and to watch them taking shape: Steven Tait adjusts the scanning tunneling microscope, contained within a steel vacuum chamber.

In the beginning, all was chaos – that much is certain. Four billion years ago, the Earth was still a hot sphere orbiting the Sun. Thousands of volcanoes spewed out the pent up heat. Red-hot magma shot out of hundreds of craters and crept across the quaking plains. Like fermenting dough, the young planet sweated out carbon dioxide, water vapor, methane and ammonia – a lethal mixture – into its thin atmosphere. Comets rained down and buried themselves deep in the Earth’s crust, colliding with such force that entire rock cliffs melted. Then, very slowly, the raging globe began to settle down.

At some point in the millions of years that followed, something amazing occurred: the eclectic mix of small molecules in the Earth’s gaseous envelope organized itself into larger structures, then into long chains, then the messenger molecule RNA, amino acids, and finally, the first primitive life forms – bacterial threads. No one knows just what happened between the archaic chaos and the dawning of life some 3.8 billion years ago. We don’t even know where the Earth’s water comes from. Was the water vapor that hissed out of the planet’s seams and cracks enough to fill the ocean basin? Or did the water reach the Earth by piggyback in the form of ice on a frosty comet?

No researcher in the world has yet managed to convincingly explain how the prehistoric jumble of molecules changed into well-ordered structures. Stanley Miller was one of the first scientists to re-enact in a laboratory what might have happened on our planet long ago. In 1953, at the University of Chicago, Miller trapped ammonia, methane, water vapor and hydrogen in a flask. For days, he sent electrical charges through the mixture to stimulate the gases to undergo chemical reactions. Miller expected a variegated cocktail of organic compounds. Instead, he found something quite astonishing: amino acids. The hostile primordial mixture had produced the building blocks of life.

Initial Encounter in the Primordial Atmosphere

Miller’s experiment was followed by many others that were intended to explain what the primordial atmosphere might really have looked like and how the first larger structures could have been created from the simple molecules. Clearly, at some point, the individual small building blocks of life must have found each other to form proteins, RNA and DNA. It was certainly not chance that brought them together, but rather the principle of self-organization. This is what forms the basis of life processes – and most certainly its genesis.

For a long time, however, no one was able to actually watch the molecules as they whirred around each other, came into contact and finally joined together to form a larger structure. The self-organization of matter remained a mystery. There simply was no device with which the dance of the molecules could be observed. But that has now changed. Many labs now have equipment that allows researchers to zoom into the world of atoms and molecules – the scanning tunneling microscope.

Phenomena in the nanoworld fascinate chemist Klaus Kern. He studies, among other things, the conditions under which molecules group together to form ordered structures.

In Klaus Kern’s labs at the Max Planck Institute for Solid State Research in Stuttgart, there is not just one, but several of these stately stainless steel apparatuses. They look like a cross between a car engine and a satellite. Small, fat portholes are used to look into a space into which a thin metal wire protrudes – the microscope’s scanning tip, a sort of molecule antenna. With this device, Kern and his colleagues observe, right down to the atomic level, how molecules on a surface arrange to form intricate patterns measuring just a few nanometers (millionths of a millimeter).

“We want to find out how self-organization works, what interactions cause a well-ordered structure to form as if from small Lego blocks.” Kern knows that he will not be able to use this to explain the evolution of life – nor is that his main concern. He is much more interested in the forces behind it: “Both evolution and the formation of molecular nanostructures are based on recognition mechanisms between molecules that join together systematically. We want to understand the underlying principles.”

A Rollercoaster Ride on the Surface

The scanning tunneling microscope is the ideal instrument for this. Its electrically conductive tip traverses the peaks and valleys of a sample. The tip does not actually touch the sample surface, but if the tip and sample come to within a few tenths of a nanometer of each other, their quantum-mechanical states overlap. This allows electrons in the sample to “jump” across the gap – a process physicists call “tunneling.” This tunnel current is especially sensitive to changes in distance, so the microscope can use it to produce an image or map of the individual molecules and atoms at the sample surface – a breathtaking peek into the nanoworld.

Like other researchers, Kern has been working with scanning tunneling microscopes (STMs) for more than 15 years. Over the years, he has refined the devices and has developed several of his own. Several of Kern’s microscopes are designed to work at an ice-cold minus 272 degrees Celsius – just a few degrees above absolute zero – where special physical phenomena can be observed. Other microscopes in Kern’s department are designed to operate just as well at plus 200 degrees as they do at the extremely cold temperatures. Kern can vary the temperature range as desired and watch his molecules at near absolute zero or at baking temperature. And that’s not all: In the central chamber of the devices, the researchers bring various substances together and watch them all simultaneously. From small secondary chambers, they shoot atoms and molecules onto a metal surface.

A few months ago, Klaus Kern and his colleagues Steven Tait, Alexander Langner and Nian Lin landed a coup. Like a lion tamer in a circus tent, they made the molecules do their bidding: in the microscope, as if led by an invisible hand, iron atoms and various organic molecules lined up to form nanometer-fine, well-ordered grids, resembling molecular rope ladders. Previously, researchers had allowed no more than two building blocks into the arena together, which joined together relatively easily to form a neat pattern. The researchers in Stuttgart, however, sent an entire mixture into the chamber: iron atoms as the central crosspoints of the grid, oblong carboxylic acids with oxygen-containing append-ages and elongated bipyridines with nitrogenous rings.

First, iron atoms, organic dicarboxylic acids and bipyridines fly through the vacuum chamber to the sample, where they land in a confused and random mess. Then, as if directed by an invisible hand, they arrange themselves into a regular grid on the copper surface, which the Stuttgart-based researchers prove with the scanning tunneling microscope image.

Steven Tait turns the scanning tunneling microscope on. Bopp-bopp, rattle the pumps, sucking the air out of the chamber. An “ultra-high” vacuum – thousands of times cleaner than in the vacuum chambers of computer chip manufacturers. Steven Tait relates tales of interminable test series, of the search for the optimum temperature and the right organic molecule. It was months before he and his team finally determined the combination in which he needed to shoot the individual molecules and iron atoms into the vacuum chamber and onto the copper surface. Atom after atom, molecule for molecule, shot through the vacuum space to the waiting sample. Then, finally, they succeeded: the mixture formed the fine grid pattern on the copper crystal.

Prior to this, Tait and his partners at the Forschungszentrum Karlsruhe had planned the design of molecules that would unite with iron to form a high-precision pattern. Tait finally decided on the carboxylic acids and nitrogenous pyridines. Changes in the mixture resulted in different appearances of the grid. In some cases, the pyridine proved to be quite elastic and also tolerated molecules that were incorporated incorrectly. The grid was slightly distorted at such sites.

Molecules Find Their Place

With a different molecule mixture on the surface, the grid was less tolerant. It automatically exchanged the molecules until everything finally fit perfectly and the defects were repaired. Just as if a set of Lego blocks were to join together on their own to build a police station and replaced any blocks that were in the wrong place. “For the first time, we were able to directly observe molecular self-selection driven by the binding energies or the stability of molecular super-structures,” says Steven Tait. “It’s fascinating: remarkably simple molecules recognized each other and organized themselves as if they had built-in programming to control self-organization and selection.”

If we could program the molecules correctly, we could form any pattern we want, and with these experiments, we are learning how to do so, Tait concludes. This is very reminiscent of the apparent intelligence of natural self-organization: for millions of years, RNA and DNA have carried within them the information of all living creatures. They are composed of just four different building blocks, and yet, through self-organization, this leads to an astounding array of species. Such processes follow the bottom-up principle, which holds that matter structures itself from tiny building blocks.

The semiconductor industry would love to apply this principle, too. It dreams of having nanostructures, components and transistors grow bottom-up on computer chips. Currently, silicon chips are created in the opposite direction – top-down. Small structures are etched in the silicon disk – the wafer. The miniaturization of these patterns, which facilitates ever more powerful chips, is now reaching its limits. Growing microscopic components through self-organization does have a certain charm.

Steven Tait uses a scanning tunneling microscope to study how molecules organize themselves to form regular structures. His colleague Magalí Lingenfelder uses this instrument to research how chiral molecules recognize each other.

The Right Mesh for Every Gas

Structures like those the researchers in Stuttgart have now created could one day serve as sensors for gases, says Steven Tait. The width of the nanogrid mesh could be changed by varying the length of the molecules. Tait’s idea: set the appropriate mesh size for each gas molecule. Such structures would also be suitable as a catalyst surface for chemical processes between certain molecules, but Klaus Kern points out that industrial bottom-up methods are still a long way off. “I’m just impressed at how simple but effective nature is,” says Kern. His colleague Magalí Lingenfelder is also studying one of these universal and, at first glance, simple natural phenomena – the chirality, the “handedness,” of molecules. If we put both hands on a table with palms facing down, we cannot bring the left and right hands into congruence.

It is the same with chiral molecules. Their chirality is determined by the position of the ligands – the attached molecule groups. Chemists differentiate between a D-form and an L-form, depending on the arrangement of the appendages. Only molecules of the same chirality fit together and react with each other. Much like when we shake hands, only the right hand can properly grip the other person’s right hand. There are some striking differences between the characteristics of chiral molecules: In the blue flowers of a sage variety, flavone pigments with a dependent D-sugar radiate in bright indigo. The same flavone molecule with an L-sugar brings forth at most a soft baby blue.

Who will take the first step? Two chiral di(phenylalanine) molecules approach each other, cautiously at first. In their mating dance, the chiral molecules adapt their form to each other and in this way build long chains.

Experts are still puzzling over why only one form of chiral molecules occurs in living creatures. Organisms always incorporate only L-amino acids in their proteins and D-sugars in the large biomolecules DNA and RNA. Why evolution favors L-amino acids and D-sugars has been a subject of dispute for decades. Lingenfelder takes her own approach to the chirality puzzle.

The Dance of the Molecules

Just as some people watch birds during mating, she watches the reactions of chiral molecules in the scanning tunneling microscope. A few months ago, she was witness to the dance of two chiral molecules and took images of their convergence at intervals of just a few seconds. In addition, she evaluated simulations performed by colleagues at King’s College London. In this way, Lingenfelder proved what Nobel laureate Linus Pauling already postulated more than 60 years ago: chiral molecules do not simply dock onto each other. Instead, they entwine each other more like a couple dancing. They drift toward each other, push each other away, change their posture, and finally, when they are in the right position, embrace each other. The researchers called this “induced fit”. Lingenfelder showed that Pauling was right, and thus provided another tile in the mosaic of our understanding of chirality.

Unlike his colleagues Lingenfelder and Tait, Alexander Bittner, also a member of Klaus Kern’s nanoscience research group, makes do without a scanning tunneling microscope. He examines the self-organization of matter in vitro and under the electron microscope. Bittner’s most important test object is the tobacco mosaic virus, which poses no harm to humans. It consists of one RNA strand that is coated with 2,100 identical proteins – a 300-nanometer-long molecular pig in a blanket.

Viruses are one of the Earth’s most efficient reproduction machines. They infect cells, unpack their genetic material, reprogram the DNA of their host for virus production and, in this way, multiply with frightening speed – a brilliantly simple principle. The tobacco mosaic virus is the best-analyzed plant virus in the world. Nevertheless, Alexander Bittner, his colleagues and biologist Christina Wege from the nearby University of Stuttgart have new plans for it. They are using it as a self-organizing raw material for components measuring just a few nanometers.

Their trick: as soon as the experimental solution reaches the right pH value and temperature, the protein subunits attach to the RNA strand. Within minutes, the RNA spiral is enveloped. The researchers have now succeeded in attaching citrate-coated gold particles to the ends of the virus, where they are held in place by a flap of RNA. It was enough to mix some gold particles and virus components together – the mixture formed into nanodumbbells all by itself. In another experiment, the virus served as a matrix for nanometer-thin wires. They succeeded in growing the protein shell without an RNA backbone, and in filling the cavity with nickel atoms – potential nanoelectronic components for the distant future.

A virus adorned with gold: A gold particle, seen here as a golden sphere, attaches to the end of the tobacco mosaic virus.

Pillars Grow in the Magnetic Field

The researchers in Stuttgart are currently working on metal-coated virus rods for ferrofluidics: For several years, magnetic particles have been used to change the viscosity of fluids. In the magnetic field, the particles form small pillars or chains. These pillars can buffer shocks. Ferrofluids are thus especially interesting as shock absorbers. However, the pillars composed of small, loosely bound particles are sensitive to strong movements. Agitation quickly annuls the cushioning effect of such a fluid. Alexander Bittner now wants to replace the chains composed of the loosely bound particles with elongated ferromagnetic nanowires from his virus workshop. The rods should be better able to withstand the shear forces.

“Viruses, and especially their RNA, are wonderful tools,” says Bittner. “The RNA simply works well.” Unlike DNA, it does more than just store information. It is simultaneously a workhorse that, similar to proteins, participates directly in metabolism. It is probably one of the first complex molecules from primordial times that kept self-organization evolving even before proteins and DNA ever entered the scene. Simple, fast and effective – for Bittner, those are the most important characteristics of his virus nanoproduction systems. Even if we do not yet fully understand the self-organization of matter and its role in evolution, the researchers in Stuttgart have been using it with great success.