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2013 JDRD Features


sarles_2Sarles, Ph.D. graduate student Graham Taylor, and ORNL’s LDRD team leader Shuo Qian have singled out cholesterol in the cell membranes of nerve cells in the brain as a possible source for answers about Alzheimer’s disease. Cholesterol is prevalent in all cell membranes, Sarles says, most especially in nerve cells (neurons) in the brain.

Exactly what triggers Alzheimer’s and the ultimate death of the brain’s neurons is the subject of intense study. Research has shown that clumped fibrils formed by amyloid beta (Aß) peptides may be accumulating in such a way as to alter nerve cell permeability—specifically the cell’s ability to move calcium ions in or out through the membrane. How the disease’s progression is influenced by cholesterol or other elements within the membrane remains in question.

“Cholesterol, itself, is known to make the cell membrane more elastic,” Sarles says. “[Cells] are fluid structures to begin with; adding cholesterol to the membrane increases their fluidity. So we think it might actually help other molecules wiggle their way in and out of the cell. But, we know little about cholesterol’s role in Alzheimer’s.”

Sarles’ team evaluates the effects Aß peptides have on the permeability of two converging cell membranes that have been synthetically filled with cholesterol molecules. They will use a molded polymer tool Sarles invented to create artificial membranes between two simple water droplets submerged in oil. The method allows them to control the fine details of membrane composition, size, hydration, and other properties—historically a difficult task to accomplish.

“Cell membranes are two molecules thick; that’s 5 nanometers or five-billionths of a meter,” he says.

His technique takes adsarles_3vantage of the fact that oil and water don’t mix. Water droplets in oil remain spherical to minimize their contact with oil. Phospholipids, the membrane’s main component, coat the water droplets; one side of the phospholipid molecule being attracted to water, the other to oil.

By pinching together and releasing the sides of a small flexible mold that holds their solution they bring the coated droplets into contact. “The droplets don’t merge; instead they zip together at the interface, making a droplet-interface bilayer,” Sarles says.

A current passed through electrodes inserted into each droplet tells the team when ions are being passed through the membrane. Aß peptides introduced into one of the two cells provide information about their behavior when cholesterol is, or is not, part of the membrane structure.

Sarles technique adds a unique dimension to Qian’s current approach, using new neutron scattering techniques to examine multilayered stacks, “almost like onionskins,” of phospholipid cell membranes.


JDRD project:
Single channel recordings and GISANS of amyloid-beta peptides in fully hydrated, unilamellar lipid bilayers
Andy Sarles, UT Mechanical, Aerospace, and Biomedical Engineering Department

LDRD project:
Developing Grazing Incident Small-Angle Neutron Scattering for studying the interplay between amyloid beta peptide and cholesterol in lipid bilayers
Shuo Qian, ORNL Center for Structural Molecular Biology


lukosi_1In order to achieve this ambitious goal, Lukosi and his team, including graduate student Thomas Wulz, are making use of advanced laboratory facilities and instrumentation at UT that include a hot wall Chemical Vapor Deposition system and a new Microelectronic and Thin Film Fabrication facility. They will be used to produce solid-state neutron imaging detectors that can perform at this level.

Recent funding from the National Science Foundation will support experimental investigations and modeling of a full-scale neutron imager and its full capabilities. So, as in many cutting-edge endeavors, both theory and experiment must work hand in hand to achieve success.

Lukosi’s investigations are focused on a corresponding LDRD project headed by Yong Yan at ORNL involving a broader inquiry into studies of zirconium alloy cladding under various physical conditions using both destructive and nondestructive analysis.

For Lukosi, this joint work affords the chance to build a long-term relationship at ORNL and the Spallation Neutron Source (SNS)* while undertaking neutron diagnostics at an advanced level. Because substantial funding will be required for the successful outcome of this challenging research, the project is only the beginning of many grant opportunities Lukosi is already on the path to pursue.

The ultimate result is expected to be a vastly improved neutron imager than what is currently available at SNS—not to mention a much safer world once fabrication of the detector is proven and leads to widespread use in critical applications.


JDRD project:
High spatial resolution neutron imaging sensors
Eric Lukosi, UT Nuclear Engineering Department

LDRD project:
Non-destructive evaluation of hydrided Zr cladding by in-situ neutron scattering and tomography of hydrogen
Yong Yan, ORNL Fusion & Materials for Nuclear Systems Division


laursen_3In their collaboration with LDRD lead Matthew Reuter, Laursen and his team, including graduate student Samiksha Poudyal and undergraduate Daniel Lawhon, will implement newly developed calculation techniques for advanced nanoscale catalytic materials using the Kraken supercomputer. Laursen’s expertise in experimental techniques provides the opportunity to verify and validate Reuter’s computational algorithms for simulating large nanoscale systems.

Both Laursen and Reuter hope to build the foundation for continuing collaboration between UT and ORNL in catalysis and computational nanoscience. As Reuter says, “The ability for my research to guide [Siris] Laursen’s experiments and for his research to suggest new theory showcases a high level of potential collaboration.”

Edison himself would cheer them on!


JDRD project:
Developing a fundamental framework based on Green’s function electronic structure calculations to rapidly calculate the composition and thermodynamics of ionic solid surfaces for applications in heterogeneous catalytic reactions
Siris Laursen, UT Chemical and Biomolecular Engineering Department

LDRD project:
An accurate and efficient computational methodology for simulating disordered nanoscale materials: toward the rational design of better batteries
Matthew Reuter, ORNL Computer Science and Mathematics Division and Center for Nanophase Materials Sciences


keppens_3As magical as that sounds, thermoelectric power is not a silver-bullet solution to recovering energy from the waste-heat produced by combustion engines or industrial machinery. Not only do waste-heat scenarios vary, thermoelectricity itself is not fully defined.

“Efficient thermoelectric materials require the unusual combination of poor thermal conductivity and good electrical conductivity,” says JDRD team leader Veerle Keppens.

“Electrons alone carry electricity; both electrons and the vibrations of atoms in a crystal’s lattice structure—known as phonons—carry heat. A good thermoelectric material is efficient at scattering phonons, which impedes the transfer of heat from one side of a material to the other while allowing the electrons to pass right on through,” Keppens says.

But what, exactly, hinders heat transfer is still unclear.

Keppens, PhD student Lindsay VanBebber, and ORNL LDRD team leader Olivier Delaire are looking into the influence ferroelectric properties have on atoms moving within a crystal’s lattice structure.

Ferroelectric materials have the ability to spontaneously polarize—and change their conductivity—in the presence of an electric field at specific temperatures.

keppens_2“As a whole, these materials are neutral; they have no actual charge,” Keppens says. “But,the way the tiny units inside the material are distributed makes it a little more negative on one end and a little more positive on the other”—in other words, polarized.

But, Keppens explains, this can only happen if the structure lacks symmetry.

“In a perfect crystal at absolute zero degrees, the atoms occupy well-defined positions. Raise the temperature and the atoms start to move, some differently from others. Because of that you can create peculiar lattice dynamics, depending on the structure and the atoms you put into a material.”

keppens_4In year-one the JDRD team synthesized single crystals containing a combination of lead, tin, telluride, molybdenum, and antimony and studied their physical responses with Resonant Ultrasound Spectroscopy (RUS). RUS shows when the structural change actually occurs in the material—information that adds insight into the mechanisms linking lattice dynamics with suppressed thermal conductivity.

In year two Keppens’ team will increase the temperature range of the experiments. Delaire’s team will collect neutron scattering data from crystals grown in Keppens’ lab. Together the ultrasound and neutron scattering results will help them build realistic computer simulations of the unusual lattice dynamics found in thermoelectric materials.


JDRD project:
Ferroelectric instabilities in thermoelectric materials (year 2)
Veerle Keppens, UT Materials Science and Engineering Department

LDRD project:
Improving energy efficiency in thermoelectric materials by integrating neutron scattering with supercomputing and modeling
Oliver Delaire, ORNL Materials Science and Technology Division


kraken_2In collaboration with ORNL experimenters using world-class neutron technology and supercomputing facilities applied to the signaling protein, kinase A (PKA), Tongye Shen targets the challenge of studying complex protein systems with a powerful combination of modeling, theoretical, and computational tools.

From the point of view of physics, the functions of protein molecules—and whether they act for good or ill—relate to the changing of states or configurations of those molecules. That is, how they function in a biological system depends upon how stable each configuration is and how fast the molecules make transitions between configurations. Each molecule has multiple stable configurations (or “conformations”) and a range of simple to complicated dynamics (or “conformational” dynamics).

Modern biology identifies many diseases as malfunctions at the molecular level of protein systems. Thus, understanding the mechanisms of these macromolecules is of critical importance to the bioengineering of new diagnostics and therapies for diseases.

shen_2

As a biophysicist Shen’s expertise is grounded in statistical and soft-matter physics and advanced computation. This project gives him the additional opportunity to collaborate in a multidisciplinary study of the large-scale, dynamic motions of signaling proteins using the cutting-edge technique of small-angle neutron scattering (SANS). However, we need better ways to interpret the valuable SANS observations related to flexible, large-scale motions of a signaling protein complex.

Enter Shen’s team—including post doc Ricky Nellas and undergraduate Richard Linsay—with “coarse-grained” modeling. The method sacrifices detailed information for the positive advantage of extending both the spatial scale (in terms of size or extent of dynamic motion of the signaling protein) and the time scale. While the calculations are formulated to take less than a few minutes, the approach is sensitive to small perturbations and void of sampling errors.

The complementary LDRD project headed by William T. Heller examines conformational changes in PKA with SANS and is an ideal testbed for validating and applying Shen’s statistical modeling tools to biomedical research. High-performance computer simulations led by Loukas Petridis will complement the joint effort. Both teams expect to continue their multidisciplinary collaboration both at UT-ORNL and with researchers at other institutions such as the University of California-San Diego and the University of Utah, while pursuing funding for further coarse-grained study of the dynamics of protein in complex environments and interfaces.


JDRD project:
Coarse-grained modeling of the conformational dynamics of signaling protein complex
Tongye Shen, UT Biochemistry and Cellular and Molecular Biology Department, UT-ORNL Graduate School of Genome Science and Technology, and UT-ORNL Center for Molecular Biophysics

LDRD project:
Probing the structure-function relationship in protein kinase A
William Heller, ORNL Biology and Soft Matter Division