Emulating -- and surpassing -- nature: Using DNA to build nanomaterials with desired properties

Nature is a master builder. Using a bottom-up approach, nature takes tiny atoms and, through chemical bonding, makes crystalline materials, like diamonds, silicon and even table salt. In all of them, the properties of the crystals depend upon the type and arrangement of atoms within the crystalline lattice.

Now, a team of Northwestern University scientists has learned how to top nature by building crystalline materials from nanoparticles and DNA, the same material that defines the genetic code for all living organisms.

Using nanoparticles as "atoms" and DNA as "bonds," the scientists have learned how to create crystals with the particles arranged in the same types of atomic lattice configurations as some found in nature, but they also have built completely new structures that have no naturally occurring mineral counterpart.

The basic design rules the Northwestern scientists have established for this approach to nanoparticle assembly promise the possibility of creating a variety of new materials that could be useful in catalysis, electronics, optics, biomedicine and energy generation, storage and conversion technologies.

The new method and design rules for making crystalline materials from nanostructures and DNA will be published Oct. 14 by the journal Science.

"We are building a new periodic table of sorts," said Professor Chad A. Mirkin, who led the research. "Using these new design rules and nanoparticles as 'artificial atoms,' we have developed modes of controlled crystallization that are, in many respects, more powerful than the way nature and chemists make crystalline materials from atoms. By controlling the size, shape, type and location of nanoparticles within a given lattice, we can make completely new materials and arrangements of particles, not just what nature dictates."

Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and professor of medicine, chemical and biological engineering, biomedical engineering and materials science and engineering and director of Northwestern's International Institute for Nanotechnology (IIN).

"Once we have a certain type of lattice," Mirkin said, "the particles can be moved closer together or farther apart by changing the length of the interconnecting DNA, thereby providing near-infinite tunability."

"This work resulted from an interdisciplinary collaboration that coupled synthetic chemistry with theoretical model building," said coauthor George C. Schatz, a theoretician and the Charles E. and Emma H. Morrison Professor of Chemistry at Northwestern. "It was the back and forth between synthesis and theory that was crucial to the development of the design rules. Collaboration is a special aspect of research at Northwestern, and it worked very effectively for this project."

In the study, the researchers start with two solutions of nanoparticles coated with single-stranded DNA. They then add DNA strands that bind to these DNA-functionalized particles, which then present a large number of DNA "sticky ends" at a controlled distance from the particle surface; these sticky ends then bind to the sticky ends of adjacent particles, forming a macroscopic arrangement of nanoparticles.

Different crystal structures are achieved by using different combinations of nanoparticles (with varying sizes) and DNA linker strands (with controllable lengths). After a process of mixing and heating, the assembled particles transition from an initially disordered state to one where every particle is precisely located according to a crystal lattice structure. The process is analogous to how ordered atomic crystals are formed.

The researchers report six design rules that can be used to predict the relative stability of different structures for a given set of nanoparticle sizes and DNA lengths. In the paper, they use these rules to prepare 41 different crystal structures with nine distinct crystal symmetries. However, the design rules outline a strategy to independently adjust each of the relevant crystallographic parameters, including particle size (varied from 5 to 60 nanometers), crystal symmetry and lattice parameters (which can range from 20 to 150 nanometers). This means that these 41 crystals are just a small example of the near infinite number of lattices that could be created using different nanoparticles and DNA strands.

Mirkin and his team used gold nanoparticles in their work but note that their method also can be applied to nanoparticles of other chemical compositions. Both the type of nanoparticle assembled and the symmetry of the assembled structure contribute to the properties of a lattice, making this method an ideal means to create materials with predictable and controllable physical properties.

Mirkin believes that, one day soon, software will be created that allows scientists to pick the particle and DNA pairs required to make almost any structure on demand.

The Air Force Office of Scientific Research, the U.S. Department of Energy Office of Basic Energy Sciences and the National Science Foundation supported the research.

The above story is reprinted (with editorial adaptations) from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.

Journal Reference:

R. J. Macfarlane, B. Lee, M. R. Jones, N. Harris, G. C. Schatz, C. A. Mirkin. Nanoparticle Superlattice Engineering with DNA. Science, 2011; 334 (6053): 204 DOI: 10.1126/science.1210493

A hidden order unraveled: Microscopic views on quantum fluctuations

 Fluctuations are fundamental to many physical phenomena in our everyday life, such as the phase transitions from a liquid into a gas or from a solid into a liquid. But even at absolute zero temperature, where all motion in the classical world is frozen out, special quantum mechanical fluctuations prevail that can drive the transition between two quantum phases.

Now a team around Immanuel Bloch and Stefan Kuhr at Ludwig-Maximilians University (LMU) and the Max Planck Institute of Quantum Optics (MPQ) has succeeded in directly observing such quantum fluctuations. Using a high resolution microscope, they were able to image quantum-correlated particle-hole pairs in a gas of ultracold atoms. This allowed the physicists to unravel a hidden order in the crystal and to characterize the different phases of the quantum gas. The work was performed together with scientists from the Theory Division at the MPQ and ETH Zurich. These measurements open new ways to characterize novel quantum phases of matter.

The scientists start by cooling a small cloud of rubidium atoms down to a temperature near absolute zero, about minus 273 degree Celsius. The ensemble is then subjected to a light field that severely restricts the motion of the particles along one-dimensional tubes of light aligned in parallel. An additional standing laser wave along the tubes creates a one-dimensional optical lattice that holds the atoms in a periodic array of bright and dark regions of light.

The atoms move in the periodic light field like electrons in solids. As these can be electric conductors or insulators, also the one-dimensional quantum gases can behave like a superfluid or like an insulator at low temperatures. In particular, the height of the optical lattice potential plays an important role: it determines whether the atom is fixed on a particular lattice site or whether is able to move to a neighbouring site. At very large lattice depths, each lattice site is occupied by exactly one atom. This highly ordered state is called a "Mott insulator," after the British physicist and Nobel laureate Sir Neville Mott. When the lattice depth is decreased slightly, the atoms have enough energy to reach a neighbouring site by quantum mechanical tunneling. In this way, pairs of empty and doubly occupied sites emerge, so-called particle-hole pairs. Intriguingly, these quantum fluctuations also occur at absolute zero temperature, when all movement in the classical world is frozen out. The position of the quantum-correlated particle-hole pairs in the crystal is completely undetermined and is fixed only by the measurement process.

In recent experiments, the physicists around Stefan Kuhr and Immanuel Bloch had already developed a method, which allowed to image single atoms lattice site by lattice site. The atoms are cooled using laser beams, and the fluorescence photons emitted in this process are used to observe the atoms with a high resolution microscope. Holes naturally show up as dark spots, but so do doubly occupied sites as the two particles kick each other out of the lattice in the experiment. Therefore particle-hole pairs appear as two neighbouring dark lattice sites. "With our technique, we can directly observe this fundamental quantum phenomenon for the first time," describes doctoral student Manuel Endres enthusiastically.

The physicists measure the number of neighbouring particle-hole pairs through a correlation function. With increasing kinetic energy, more and more particles tunnel to neighbouring sites and the pair correlations increase. However, when the number of particle-hole pairs is very large, it becomes difficult to unambiguously identify them. Hence the correlation function takes on smaller values. Finally, the ordered state of a Mott insulator vanishes completely und the quantum gas becomes a superfluid again. Here fluctuations of holes and particles occur independently. The correlation function measured in the experiment is very well reproduced by model calculations, which were performed by scientists from the Theory Division at the MPQ and the ETH Zurich. Interestingly, the same investigations on two-dimensional quantum-gases clearly showed that quantum fluctuations are not as prominent as in one-dimensional systems.

The scientists extended their analysis to correlations between several lattice sites along a string. Such non-local correlation functions contain important information about the underlying many-body system and can be used as an order parameter to characterize different quantum phases. In the experiment described here, such non-local order parameters have been measured for the first time. In the future, the scientists plan to use these measurements for the detection of topological quantum phases. These can be useful for robust quantum computers and could help to understand superconductivity at high temperatures. (MPQ)

Story Source:

The above story is reprinted (with editorial adaptations ) from materials provided by Ludwig-Maximilians-Universität München.

Journal Reference:

M. Endres, M. Cheneau, T. Fukuhara, C. Weitenberg, P. Schauss, C. Gross, L. Mazza, M. C. Banuls, L. Pollet, I. Bloch, S. Kuhr. Observation of Correlated Particle-Hole Pairs and String Order in Low-Dimensional Mott Insulators. Science, 2011; 334 (6053): 200 DOI: 10.1126/science.1209284

Potential new drugs plug brain's biological 'vacuum cleaner' and target HIV

 In an advance toward eliminating pockets of infection in the brain that help make HIV disease incurable, scientists report the development of new substances that first plug the biological vacuum cleaner that prevents anti-HIV drugs from reaching the brain and then revert to an active drug to treat HIV. They describe the advance, which allows medications to cross the so-called "blood-brain barrier" (BBB) and treat brain diseases, in the Journal of the American Chemical Society.

Jean Chmielewski, Christine Hrycyna and colleagues explain that Human Immunodeficiency Virus infection remains incurable because HIV can sneak through the BBB -- a network of special blood vessels and cells that protects the brain from many harmful substances -- while many of the most powerful anti-viral medications cannot. A pump at the BBB suctions anti-viral medicines away like a biological vacuum cleaner, leaving a reservoir of HIV in the brain. To overcome this hurdle and get rid of the last footholds of HIV, the researchers set out to develop a new group of drugs that can plug up the vacuuming mechanism and then sneak across the BBB to fight HIV.

Their approach involves gluing two anti-HIV drug molecules together with a "tether." This dual drug plugs up the BBB vacuum cleaner and can then sneak across the BBB. Once across, the tether disintegrates, freeing the two drug molecules to kill the virus. "This overall strategy represents a platform technology that may be readily applied to other therapies with limited brain penetration," such as anticancer and anti-schizophrenia drugs, say the researchers.

More information: Toward Eradicating HIV Reservoirs in the Brain: Inhibiting P-Glycoprotein at the Blood–Brain Barrier with Prodrug Abacavir Dimers, J. Am. Chem. Soc., Article ASAP. DOI: 10.1021/ja206867t

Abstract
Eradication of HIV reservoirs in the brain necessitates penetration of antiviral agents across the blood–brain barrier (BBB), a process limited by drug efflux proteins such as P-glycoprotein (P-gp) at the membrane of brain capillary endothelial cells. We present an innovative chemical strategy toward the goal of therapeutic brain penetration of the P-gp substrate and antiviral agent abacavir, in conjunction with a traceless tether. Dimeric prodrugs of abacavir were designed to have two functions: inhibit P-gp efflux at the BBB and revert to monomeric therapeutic within cellular reducing environments. The prodrug dimers are potent P-gp inhibitors in cell culture and in a brain capillary model of the BBB. Significantly, these agents demonstrate anti-HIV activity in two T-cell-based HIV assays, a result that is linked to cellular reversion of the prodrug to abacavir. This strategy represents a platform technology that may be applied to other therapies with limited brain penetration due to P-glycoprotein.

Provided by American Chemical Society (news : web)

New equation predicts molecular forces in hydrophobic interactions

The physical model to describe the hydrophobic interactions of molecules has been a mystery that has challenged scientists and engineers since the 19th century. Hydrophobic interactions are central to explaining why oil and water don't mix, how proteins are structured, and what holds biological membranes together. Chemical engineering researchers at UC Santa Barbara have developed a novel method to study these forces at the atomic level, and have for the first time defined a mathematical equation to measure a substance's hydrophobic character.

"This discovery represents a breakthrough that is a culmination of decades of research," says Professor Jacob Israelachvili. "The equation is intended to be a tool for scientists to begin quantifying and predicting molecular and surface forces between organic substances in water."

Using a light-responsive surfactant -- a soap-like molecule related to fats and lipids -- the researchers developed an innovative technique to measure or change the forces between layers of the molecule in water by using beams of UV or visible light. The result is a general equation that applies to even more complicated systems, such as cellular membranes or proteins.

"We were fortunate to find the right combination of experimental methods and theory," said Brad Chmelka, UCSB Chemical Engineering professor and co-author of the study. "The keys to our research were using a light-responsive surfactant molecule, a means of measuring these delicate surface forces, and applying knowledge of what to look for."

The highly-sensitive instrument they used to sense these molecular-level hydrophobic forces, called a surface forces apparatus, is a now-standard technique that was originally pioneered by Israelachili and colleagues in the 1970s.

"In basic chemistry, students learn about van der Waal forces -- the weak forces that act between all molecules. That theory was developed more than 100 years ago," explains Professor Israelachvili.

"According to the van der Waals theory, however, oil and water shouldn't separate and surfactants shouldn't form membranes, but they do. There has been no proven theory to account for these special hydrophobic interactions. Such behaviors are crucial for life as we know it to exist."

Hydrophobic and hydrophilic interactions are central to the disciplines of chemistry, physics, and biology that have fueled modern developments in industries from detergents to pharmaceuticals and new biotechnologies. The new equation is expected to impact applications in water filtration, membrane separations, biomedical research, gene therapy methods, biofuel production, and food chemistry.

Virus and disease propagation in the human body are directly linked to hydrophobic properties on a cellular level. One of the problems related to chemotherapy treatments for cancer is being able to direct a drug specifically to cancer cells, instead of the entire body. Israelachvili and his colleagues foresee their discovery having an impact in biomedical research that attempts to understand and treat diseases.

"Cell membranes are complex and discriminating structures, allowing the transmission of various signals into cells and mediating specific interactions with bacteria and viruses," said Jean Chin, Ph.D., who oversees membrane structure grants at the National Institute of General Medical Sciences of the National Institutes of Health. "This study, by enhancing our understanding of the role played by hydrophobic forces in membrane dynamics, will expand what we know about membrane structure and function, as well as microbial infection pathways."

"Understanding how water and oil-like substances interact is enormously important for explaining the properties and functions of many biological and engineering materials," says Dr. Robert Wellek, Program Director in the Directorate for Engineering at the National Science Foundation. "The UCSB and USC teams have elegantly combined concepts from synthetic chemistry, photophysics, and chemical engineering to unravel and quantify the elusive hydrophobic interaction. NSF is very pleased that its grantees have been able to contribute important fundamental knowledge in this important area."

Details of the research were published this month in the Proceedings of the National Academy of Sciences. Their research was made possible by support from the National Science Foundation, the National Institutes of Health, and the Procter & Gamble Company.

"We've known for a long time what we were aiming for. It's a bit like climbing a mountain," said Professor Israelachvili. "The whole thing started at the very bottom. I've been searching for the keys to this interaction for thirty years. We are thrilled with the findings, but it took a lot of steps over carefully chosen paths to get there."

Professor Jacob Israelachvili, Professor Bradley Chmelka, and Stephen Donaldson, Ph.D. student, are with the Department of Chemical Engineering at UCSB. Dr. Israelachvili is a Fellow of the Royal Society of London and member of the U.S. National Academy of Science and the U.S. National Academy of Engineering. Dr. Israelachvili received his Ph.D. in Physics from University of Cambridge and joined UCSB in 1986. He was recently named by the American Institute of Chemical Engineers as one of the "100 Chemical Engineers of the Modern Era" for his achievement and leadership in the field.

 

The above story is reprinted (with editorial adaptations ) from materials provided by University of California - Santa Barbara, via EurekAlert!, a service of AAAS.

Journal Reference:

S. H. Donaldson, C. T. Lee, B. F. Chmelka, J. N. Israelachvili. General hydrophobic interaction potential for surfactant/lipid bilayers from direct force measurements between light-modulated bilayers. Proceedings of the National Academy of Sciences, 2011; 108 (38): 15699 DOI: 10.1073/pnas.1112411108