October 23, 2014
by Benjamin Recchie, AB'03
The research of Juan J. de Pablo, the Liew Family Professor in Molecular Engineering, touches on DNA, microelectronics, diseases, light-emitting diodes, and even glue. What’s the common thread? They’re all aspects of his overarching research interest, he says: “To be able to understand, predict, and design the behavior of soft materials from first principles.”
Soft materials, de Pablo explains, are those in which the interactions between the constituents are sufficiently weak that you can perturb them with relatively modest forces. (Think of plastic, a gel, or a living cell.) “Because you can so easily perturb the structural properties of these materials, coming up with models that can capture all their behavior is very, very difficult,” he says.
Organic glass
Most people wouldn’t define glass as “soft,” but de Pablo points out that glass does flow, even at room temperature—just incredibly slowly. His group is interested not in the kind of glass that you find in a window, but a recently discovered variety made of organic materials, created by depositing molecules one at a time on a surface. Creating an organic glass this way can result in a material with surprising properties, such as stiffness, mechanical stability, and “high efficiency in organic light-emitting diodes”—much more efficient and stable than existing technology.
So far, organic glasses have only been manufactured by trial and error. De Pablo is trying to simulate all the interactions inside the material to understand how its physical properties come to be—and how to reproduce them.
Coacervates
When polymeric molecules have an electric charge, they tend to form aggregates of materials that interact strongly with each other. But recently scientists have discovered that under some circumstances the charged molecules will interact with each other but not aggregate. Called coacervates, they have the interesting property of having no interfacial tension. This means a drop of coacervate won’t bead up on a surface like water does; instead, it will spread into even the tiniest pores.
“Calculating [coacervates’ behavior] is complicated,” says de Pablo. “You have electrostatic interactions over long ranges, and a competition between several types of forces. There are no theories for that.” The only way to understand the interactions between the molecules is to simulate them. If scientists can understand that, de Pablo says, engineers could put them to work as a glue that works underwater, or recovering oil from oil spills.
DNA simulation
One of big mysteries of DNA, says de Pablo, is how a meter-long strand of the stuff can be rolled into a tiny sphere small enough to fit into the nucleus of a cell. When a cell wants to wind the DNA up, it wraps the strand around proteins called histones. The strand coils around each histone twice. Then the coils themselves wrap around to form coils of coils, then larger coiled structures, until the entire strand is wrapped up in a ball just a few microns across–a chromosome.
The mechanics of this coiling process are hard to tease out, as is the hierarchy of the structures; high-powered computing is the only way to simulate the interactions between the millions of molecules of DNA . But de Pablo points out that the enzymes that read DNA to produce proteins can more easily access the parts of the DNA that aren’t wrapped around the histone coils. How the DNA “knows” to keep those sections available is still a bit of a mystery. “You want to understand which regions are available and which are blocked,” he says. “Then you can start to understand genetics at a truly molecular level.”
Disordered peptides
There are classes of proteins in the human body that are normally completely disordered, free-floating and exhibiting no structure. But sometimes those proteins start to fold in a certain way that causes them to aggregate into fibers, structures which have been linked to type 2 diabetes, Alzheimer’s disease, and Huntington’s disease. Unfortunately, scientists don’t understand well how or why these fibers form, nor how to prevent or get rid of them. De Pablo and his group are using intensive simulation to study how these peptides fold, aggregate, and interact with substances known to alleviate disease symptoms in tests—the first steps towards cures.
Block copolymers
In their simplest form, block copolymers are polymeric molecules that are composed of two different materials joined in the center. When put in solution, each material attempts to be near similar materials from the other molecules. (Think of pairs of men and women entering a room while holding hands. If the men want to be with the other men and women with the other women, but neither wants to let go, they’ll form big clumps of each gender next to each other.) This segregation leaves lamella—thin layers of one material alternating with the other.
“You have a material that, to naked eye, looks completely homogeneous,” says de Pablo. “But if you had an incredibly powerful microscope, you would see stripes that measure 20 nm across.” If scientists could then selectively remove one of the copolymer materials and replace it with gold, they could lay down in incredibly compact electric circuit—a possibility that has semiconductor manufacturers such as Intel eager to learn more.
The trick is to learn how to guide and control the assembly of the structures into shapes that are useful for circuits; de Pablo’s group is using highly detailed simulations of the interactions between the molecules to learn how to manipulate their assembly and avoid the formation of defects that could ruin a circuit.
Liquid crystals
“Liquid crystals are interesting in that they are examples of a material that has order over short length scales but none over long length scales,” explains de Pablo. One of their interesting properties is that a perturbation of the liquid crystal on the scale of a few nanometers can be amplified over distances of microns—a thousand times farther, or more. De Pablo describes the possibility of using this property as the basis of an improved detector for very small objects, such as a protein or a virus: “I can have a single molecule binding at the interface of a liquid crystal, and I can observe a response of a liquid crystalline material with a simple optical microscope. It is the ultimate detector.”
However, to build and optimize a device with that sensitivity, researchers must first be able to prepare the liquid crystal very carefully. “Theory isn’t accurate enough to give that,” he says. As with all of the other research areas mentioned above, “the only way to cover all the complex interactions inherent in soft materials is to simulate them using high-performance computing.”
De Pablo, his collaborators, and his research group have used the resources of the Research Computing Center extensively, to the tune of seven million hours of CPU time in the past year alone. And they've clearly put that time to good use: RCC resources contributed to 28 papers that the de Pablo group submitted, accepted, or published in major scientific journals in that same time frame. The science may be small, but the results are big.