For most of us, crossing borders is something we do on an occasional international trip a visit to Rome's Colosseum perhaps, or China's Great Wall. For Sam Stupp, that's just the beginning. A native of Costa Rica and a lover of travel, Stupp spends plenty of time on planes traversing lines drawn on maps. But his greatest border crossings come in his lab at Northwestern, where together with his students, he continuously blurs the lines between the normally autonomous disciplines of chemistry, physics, materials science and biology.
Stupp (GMcC77), Board of Trustees Professor of Materials Science, Chemistry and Medicine and a professor of chemistry, specializes in designing molecules that under the right conditions spontaneously assemble into tiny objects, which themselves go on to coalesce into even bigger structures. This multiple-level self-organization isn't just arcane chemistry brewed up at the bench. It's found throughout life and is central to the construction of everything from cell walls and bones to muscles and teeth.
That has made Stupp's specialty of molecular self-assembly one of the hottest areas in chemistry today, and one that many researchers believe holds the future for nascent fields ranging from nanotechnology to tissue engineering. Advancing the frontiers of self-assembly requires working in an area that falls between traditional academic disciplines, just the place Stupp prefers to spend his time.
"Sam has always been a person who has blended fields. I would describe him as almost fearless in that regard," says Jeff Moore, a former graduate student of Stupp's at the University of Illinois at Urbana-Champaign and now a professor of chemistry there. Few researchers are comfortable working outside their own discipline, he adds. Most tend to master one discipline and then team up with other groups to collaborate on questions that span fields. Stupp, on the other hand, prefers to select graduate students and postdoctoral research assistants with a broad range of talents to work in his lab and then set them loose on projects of mutual interest.
This interdisciplinary approach can be fraught with peril if lab work stagnates as people spend all their time trying to come up to speed on unfamiliar topics. But Stupp is one of the few who manage to pull it off, says Moore. He does it all and does it all well.
Others seem to agree with Moore. In December Stupp earned the prestigious MRS medal from the Materials Research Society for his work on self-assembly. Three years ago Northwestern lured him away from the University of Illinois, in part to head a new interdisciplinary center at Northwestern the Institute for Bioengineering and Nanoscience in Advanced Medicine which aims to apply the advanced tools of physics and chemistry to engineering and medicine.
In Search of a New Home
Sam Stupp grew up bridging cultures. Both his parents moved to Costa Rica from Eastern Europe as children shortly before World War II. And although Stupp today looks more like former German chancellor Helmut Kohl than Ricky Martin, his soul is Latin to the core. He enjoys Latin American culture and pines for the natural beauty of his homeland.
It was his passion for science discovered in his earliest school days that tore him away from Central America. After graduating from high school, he moved to Southern California, where his aunt lived, to attend the University of California, Los Angeles. He never went back.
"Originally I planned on returning to Costa Rica, so I thought I should study something practical, such as chemical engineering," Stupp says. At the time UCLA didn't offer it, so Stupp settled on chemistry. But even as he was getting his feet wet, Stupp's interests at UCLA swept him away from the field's mainstream.
At the time, chemistry was under the sway of icons such as Linus Pauling, who preached the need for understanding the workings of individual molecules, particularly small molecules that could be characterized in great detail. Stupp on the other hand found himself drawn to more unwieldy large molecules, such as the long, spaghetti-like polymer chains at the heart of plastics.
"Chemists were not interested in polymers" at the time, Stupp says. Most looked down their noses at them, arguing that they were better left to the engineers, as their haphazard lengths and arrangement made them too loosely defined for meaningful study. But as plastics, polymers were beginning to make a big difference in people's lives. That fact enticed Stupp to study polymers as solo molecules and in groups. The latter endeavor, which later came to be known as materials science, was another young field in which few scientists were interested at the time.
"I remember reading something in the New York Times as an undergraduate about materials science as a new field," says Stupp. So as he neared completing his degree at UCLA he asked his professors where he should go to pursue the topic in graduate school. "They recommended Northwestern," which established the first materials science program in the world, says Stupp. "Northwestern basically defined the field."
During his first go-round at Northwestern, Stupp not only studied his pet topic of macromolecules, he also pursued research in the physics of artificial cell membranes, establishing early on a pattern of interest in multiple fields. After earning his doctorate and teaching briefly at Northwestern while his wife, Dévora (WCAS76, G83), completed requirements for her doctorate in political science, Stupp joined the faculty at Illinois in 1980.
Molecule, Assemble Thyself
At Illinois Stupp started working on liquid crystalline molecules, rod-shaped organic compounds that can respond strongly to external stimuli such as light and electric fields. These external stimuli cause the molecules to interact with one another, changing from random orientation to lining up like a stack of pencils.
The molecules basically arrange themselves, a process chemists call molecular self-assembly. Today, makers of laptop computers harness that property in liquid crystals to filter out different colors of light in the thin displays. "It's the assembly [the stack of liquid crystalline molecules] that generates the function, not the individual molecules," says Stupp. "I thought that was really fantastic."
The phenomenon was so special in fact that Stupp wanted to see if he could design his own molecules to mimic the ability of liquid crystals to self-assemble. He decided to take on a problem that had bedeviled polymer researchers for years: making polymers shaped as flat sheets. Because polymers are big molecules, most are simply long, floppy chains that blend together in a confusing tangle similar to a pot of cooked spaghetti. Stupp wanted to see if he could make a polymer in a different way, by starting with shorter rod-like molecules that would line up side by side and then link up in a continuous sheet. Other scientists had tried different strategies but failed.
Stupp constructed the molecular rods, called oligomers, so that each contained a pair of reactive chemical groups, one in the middle, the other on one of the ends. The oligomers were designed to assemble by themselves so that pairs of reactive end groups would face each other like two pencils joined end to end at the erasers; additional oligomer pairs then nuzzled up alongside, forming a sheet.
Stupp's team then added specialized linking compounds to forge bonds between both the "eraser" groups at the ends of the oligomers and between the reactive groups in the middle of the molecules. As a result the billions of molecules in the parallel sheets stitched themselves together. In a commentary published in Science in 1993, Edwin Thomas, Morris Cohen Professor of Materials Science at the Massachusetts Institute of Technology, lauded the creations as the first "gigamolecules in flatland."
Challenging the Engineers
Self-assembling plastic sheets have yet to have much of a commercial impact, since it's easy enough for today's plastics makers to form sheets and films in other ways. But Stupp's discovery could have enormous impact on the nanotechnologies to come in the 21st century.
The early work convinced Stupp that self-assembly could perform feats that engineers couldn't touch. To prove it, he decided to take on one of the most heavily engineered materials around: semiconductors, the materials at the heart of computer chips. When computer chip makers construct the processing chips that run a computer, they start with salad plate-sized wafers of silicon the actual semiconductor. They then use a painstaking process called photolithography to pattern a network of wires and other components on the chips. Yet as crucial as photolithography is to the entire process, it has severe limitations, not the least of which is that billion-dollar chip-making plants are needed to make wires and other features about 200 billionths of a meter a nanometer across. While that's just a fraction of the width of a human hair, it's gigantic compared to the size of molecules.
Stupp and his students thought they could do better, shrinking features to the molecular scale. They designed two-part molecules, one half made from a water-friendly, or hydrophilic, compound, and the other from a hydrophobic group that flees water. When they added these two-part molecules to a watery bath, the hydrophobic groups on separate molecules clumped together, forming cylinders to try to hide themselves from the surrounding water. And with the right mix of starting materials, the cylinders arranged themselves into a honeycomb pattern.
To this array of cylinders, Stupp's team members added a new batch of water-loving compounds that sought out the watery region around the cylinders. After they added yet another compound to the mix, the stew of compounds in the watery region joined up to form a common semiconductor. Then using a solvent to wash out the hydrophobic cylinders, they were left with a thin semiconductor film pocked with an array of holes, each the size of 2 nanometers, a level of patterning resolution that photolithography cannot approach. While such films remain a long way from a Pentium chip, Stupp's lab has since gone on to investigate their use as the basis for everything from highly efficient solar cells and molecular sieves to advanced medical devices.
Stupp's team was just warming up. Next, they designed another set of two-part molecules that carried self-assembly to a new level of sophistication. The molecules, dubbed rodcoils, contained one rigid portion resembling a molecular rod joined at one end to a more flexible coil. On the free end of the rods, Stupp's team added a sticky organic group called a pheolic group, while capping the coils with a slippery compound called a methyl. Stupp and his students were hoping to get their two-part molecules to line up side by side to form a continuous layer with all the molecules pointing the same way, as with their polymer sheets. If it worked, that would make one surface of their sheet sticky and the other slick.
They got the result they were looking for. But the assembly wasn't as simple as they first imagined. At the smallest scale, groups of about 100 rodcoils aggregated into mushroom-shaped clusters, with the rodcoils' rigid ends forming the stems and the flexible coils forming the caps. The mushrooms take shape, says Stupp, because an attractive force between the rods draws them together, while the bulky coils push each other apart. When the clusters are very small, the attractive force between the rods dominates, so as a result the mushrooms grow until they are about 5 nanometers across before the repulsion between the coils prevents them from getting any bigger.
But the fun didn't stop there. The mushrooms, it turns out, pack side by side stems down, caps up, forming sheets. Then these sheets stack in layers, with the stems riding atop caps, to form thick films. Stupp is still trying to solve the mystery of just why the films assemble in this manner: He expected the mushrooms to alternate pointing up and down to save space. Nevertheless, the films' unique arrangement gives them their separate slick and sticky surfaces, a property that others are now looking at for use as thin coatings on aircraft to prevent ice from sticking on the wings.
Stupp's nano-sized mushrooms could find other uses as well. He and his team are adding different chemical appendages to their stems and caps, looking for ways to use the mushrooms to deliver drugs within the body, create artificial receptors for cells and even serve as scaffolds for growing new tissues.
"The mushroom-based films stand out as one of the first examples of designer molecules that form precisely sized nano-structures all by themselves," says Paul Braun, another former student of Stupp's who now also runs his own group at the University of Illinois.
"It points to a new direction in science. And that's where [Stupp] likes to work," says Braun. Stupp agrees. "I love breaking new ground. I think that's the ultimate dream that a scientist can have," he says. "To me that's more interesting than taking one idea and championing it to make it more and more useful."
Stupp plans to continue breaking ground at his new home at Northwestern. He makes it clear that his decision to return to his alma mater from Urbana goes beyond the offer to run the new interdisciplinary center and the chance to work in a new lab specifically designed for his border-crossing research. "I'm working on a lot of things that are hybrids at the interface between biology, materials science and chemistry," says Stupp. Northwestern administrators "gave me the opportunity in many ways, including access to research funds, that are very difficult to get for high-risk research."
And unlike his usual travel experience, he didn't even have to cross a state or national border to make the trip.
Bob Service is a Seattle-based staff writer for Science magazine.