North Western U: Study Provides insight into how Nanoparticles interact with Biological Systems

Computer simulation of a lipid corona around a 5-nanometer nanoparticle showing ammonium-phosphate ion pairing. Credit: Northwestern University

Personal electronic devices—smartphones, computers, TVs, tablets, screens of all kinds—are a significant and growing source of the world’s electronic waste. Many of these products use nanomaterials, but little is known about how these modern materials and their tiny particles interact with the environment and living things.

Now a research team of Northwestern University chemists and colleagues from the national Center for Sustainable Nanotechnology has discovered that when certain coated  interact with living organisms it results in new properties that cause the nanoparticles to become sticky. Fragmented  coronas form on the particles, causing them to stick together and grow into long kelp-like strands. Nanoparticles with 5-nanometer diameters form long structures that are microns in size in solution. The impact on cells is not known.

“Why not make a particle that is benign from the beginning?” said Franz M. Geiger, professor of chemistry in Northwestern’s Weinberg College of Arts and Sciences. He led the Northwestern portion of the research.

“This study provides insight into the molecular mechanisms by which nanoparticles interact with biological systems,” Geiger said. “This may help us understand and predict why some /ligand coating combinations are detrimental to cellular organisms while others are not. We can use this to engineer nanoparticles that are benign by design.”

Using experiments and computer simulations, the research team studied polycation-wrapped gold nanoparticles and their interactions with a variety of bilayer membrane models, including bacteria. The researchers found that a nearly circular layer of lipids forms spontaneously around the particles. These “fragmented lipid coronas” have never been seen before.

The study points to solving problems with chemistry. Scientists can use the findings to design a better ligand coating for nanoparticles that avoids the ammonium-phosphate interaction, which causes the aggregation. (Ligands are used in nanomaterials for layering.)

The results will be published Oct. 18 in the journal Chem.

Geiger is the study’s corresponding author. Other authors include scientists from the Center for Sustainable Nanotechnology’s other institutional partners. Based at the University of Wisconsin-Madison, the center studies engineered nanomaterials and their interaction with the environment, including biological systems—both the negative and positive aspects.

“The nanoparticles pick up parts of the lipid cellular membrane like a snowball rolling in a snowfield, and they become sticky,” Geiger said. “This unintended effect happens because of the presence of the nanoparticle. It can bring lipids to places in cells where lipids are not meant to be.”

The experiments were conducted in idealized laboratory settings that nevertheless are relevant to environments found during the late summer in a landfill—at 21-22 degrees Celsius and a couple feet below ground, where soil and groundwater mix and the food chain begins.

By pairing spectroscopic and imaging experiments with atomistic and coarse-grain simulations, the researchers identified that ion pairing between the lipid head groups of biological membranes and the polycations’ ammonium groups in the nanoparticle wrapping leads to the formation of fragmented lipid coronas. These coronas engender new properties, including composition and stickiness, to the particles with diameters below 10 nanometers.

The study’s insights help predict the impact that the increasingly widespread use of engineered nanomaterials has on the nanoparticles’ fate once they enter the food chain, which many of them may eventually do.

“New technologies and mass consumer products are emerging that feature nanomaterials as critical operational components,” Geiger said. “We can upend the existing paradigm in nanomaterial production towards one in which companies design nanomaterials to be sustainable from the beginning, as opposed to risking expensive product recalls—or worse—down the road.”

 Explore further: Water matters to metal nanoparticles

More information: “Lipid Corona Formation from Nanoparticle Interactions with Bilayers,” Chem (2018). DOI: 10.1016/j.chempr.2018.09.018



“Crumpled” Graphene Balls Could Improve Batteries’ Performance by Preventing Lithium Dendrite Growth: Northwestern University


Crumpled Graphene NewsImage_36035Jiaxing Huang discovered crumpled graphene balls six years ago. (Image credit: Jiaxing Huang)

Lithium metal-based batteries have the potential to revolutionize the battery sector. With the theoretically ultra-high capacity of lithium metal used by itself, this new type of battery can be employed to power everything from personal gadgets to cars.

“In current batteries, lithium is usually atomically distributed in another material such as graphite or silicon in the anode,” explains Northwestern Engineering’s Jiaxing Huang. “But using an additional material ‘dilutes’ the battery’s performance. Lithium is already a metal, so why not use lithium by itself?”

The answer is a research challenge that scientists have spent years attempting to overcome. As lithium gets charged and discharged in a battery, it begins to grow dendrites and filaments, “which causes a number of problems,” Huang said. “At best, it leads to rapid degradation of the battery’s performance. At worst, it causes the battery to short or even catch fire.”Northwestern-Hero

One existing solution to avoid lithium’s destructive dendrites is to employ a porous scaffold, such as those made from carbon materials, on which lithium preferentially deposits. Then during battery charging, lithium can deposit along the surface of the scaffold, bypassing dendrite growth. This, however, introduces a new issue. As lithium deposits onto and then dissolves from the porous support as the battery cycles, its volume wavers significantly. This volume fluctuation causes stress that could break the porous support.

Huang and his collaborators have deciphered this problem by choosing a different approach — one that even makes batteries lighter weight and able to contain more lithium.

The answer lies in a scaffold composed of crumpled graphene balls, which can stack with ease to form a porous scaffold, because of their paper ball-like shape. They not only prevent dendrite growth but can also survive the stress from the wavering volume of lithium. The research was featured on the cover of the January edition of the journal Joule.

“One general philosophy for making something that can maintain high stress is to make it so strong that it’s unbreakable,” said Huang, professor of materials science and engineering in Northwestern’s McCormick School of Engineering. “Our strategy is based on an opposite idea. Instead of trying to make it unbreakable, our scaffold is made of loosely stacked particles that can readily restack.”

Huang discovered crumpled graphene balls six years ago.  Crumpled graphene balls are novel ultrafine particles that look like crumpled paper balls. He formed the particles by atomizing a dispersion of graphene-based sheets into minute water droplets. When the water droplets evaporated, they produced a capillary force that crumpled the sheets into miniaturized paper balls.

crumpling-graphene-electronics-Illinois-img_assist-350x197In Huang’s team’s battery, the crumpled graphene scaffold houses the fluctuation of lithium as it cycles between the cathode and anode. The crumpled balls can travel apart when lithium deposits and then freely assemble back together when the lithium is depleted. Since minute paper balls are conductive and allow lithium ions to flow quickly along their surface, the scaffold forms a continuously conductive, porous, dynamic network for lithium.

“Closely packed, the crumpled graphene balls operate like a highly uniform, continuous solid,” said Jiayan Luo, the paper’s co-corresponding author and professor of chemical engineering at Tianjin University in China. “We also found that the crumpled graphene balls do not form clusters but instead are quite evenly distributed.”

Formerly advised by Huang, Luo received his PhD in materials science and engineering in 2013. Currently as a professor and researcher at Tianjin University, Luo continues to partner with Huang.

In contrast to batteries that use graphite as the host material in the anode, Huang’s solution is a lot lighter in weight and can stabilize a higher load of lithium during cycling. While typical batteries encapsulate lithium that measures only tens of microns in thickness, Huang’s battery holds lithium stacked 150 µm high.

Huang and his collaborators have filed a provisional patent via Northwestern’s Innovation and New Ventures Office (INVO).

The National Natural Science Foundation of China, the Natural Science Foundation of Tianjin, China, the State Key Laboratory of Chemical Engineering, and the Office of Naval Research supported the research.


Shaping Stem Cell Research with Nanotechnology – Hope for Treating Parkinson’s; Heart Disease and ???

Nanoscientists have developed a technique that allows them to transform stem cells into bone cells on command. But could the process be used to treat deadly conditions such as heart disease and Parkinson’s?

Anyone who knows a thing or two about biology knows that stem cells have tremendous potential in medicine: anything from repairing and replenishing heart cells after an attack to replacing nerve cells that are progressively lost in the brain of a person with Parkinson’s.

One of the big challenges of using stem cells as a therapy is coaxing them to grow into the specific type of tissue that is required. In the body this happens thanks to precise chemical and physical signals, not all of which are yet understood or characterised.

Using chemicals to direct the fate of stem cells has worked in laboratories, but the outcomes are not always safe or predictable.

Now, a team from Northwestern University in the US thinks it has a solution. They say that they can direct the developmental fate of stem cells using only physical cues, by adapting a well-known technique that traces three-dimensional microscopic shapes and reconstructs them on flat surfaces.

The process is called scanning probe lithography.

By placing the stem cells on the nanopatterned surface, and without adding any kind of chemicals, the scientists found that they could induce the stem cells to develop into bone cells.

Extend this technique, they say, and it might be possible to turn stem cells into any type of cell on command.

When the body needs a repair to be carried out, a special type of stem cell – called mesenchymal stem cells or MSCs – can enter the blood circulation system. These cells travel around the body and actually home in on where they are needed.

MSCs have the potential to develop into a whole range of different tissue types – in other words, they are pluripotent.

The developmental decision that they make depends, in part, on the molecular structures in the matrix surrounding the cells that make up the tissue.

The structure of the matrix affects the softness of the tissue – so the brain is a soft, mushy tissue, while stiffer tissues include muscle, and rigid tissues include bone.

The US team has mimicked this real-life situation. Using the molecular structures in the matrix that surround a cell as a pattern, and with an array of pyramid-like points that are a hundred-thousand times smaller than the tip of a pencil and incredibly sharp, molecule by molecule they have built up a kind of nano-landscape with sculptures ranging in size from the nano- to the microscale, on a small piece of glass. The technique is called polymer pen lithography.

The researchers grew MSCs on one type of nanoscopic sculpture, and were able to direct their developmental fate.

“Starting with millions of possibilities, we quickly zeroed in on the pattern of features that best directed the stem cells into osteocytes [bone cells],” says Chad A Mirkin, who led the work.

Mirkin is professor of chemistry in the Weinberg College of Arts and Sciences and is also the director of Northwestern’s International Institute for Nanotechnology.

The potential of this tool is to be able to take pluripotent stem cells from a patient, run them over a selected three-dimensional matrix in order to convert them rapidly into a particular cell type of choice, and then return them to the patient for repair and replenishment of damaged tissues.

“With further development, researchers might be able to use this approach to prepare cells of any lineage on command,” Mirkin says.

“The three-dimensional aspect is very interesting, and mimics aspects of the environment in a highly stylized way,” says Fiona Watt, professor and director of the Centre for Stem Cells and Regenerative Medicine at Kings College London.

“Several reports argue that the topology imposed on a stem cell – how a stem cell is contained in 3D – affects its behaviour. When you consider your bones and cartilage, this makes perfect sense,” Watt adds.

One important aspect of this work according to Marilyn Monk, emeritus professor of molecular embryology at University College London’s Institute of Child Health, is that it provides evidence that stem-cell fate can solely be informed by the local three-dimensional molecular structure.

“But that’s not to say that this is the only way to direct stem-cell fate,” Monk says. “We know that regulation of development involves multiple mechanisms that operate independently and inter-dependently to bring about a final specific cell function.”

Nonetheless he believes the technique is a real advance. “It would be neat to see if they can take a stem cell, already committed in one developmental direction, and back it up so that it might become another type of cell again, using only their patterning technique,” he says.

“That would be the Nobel prize.”

Rice U: Nano-Shells could deliver more chemo with fewer side effects

Rice Nano shells 171108143658_1_540x360
Researchers from Rice University and Northwestern University loaded light-activated nano-shells (gold and light blue) with the anticancer drug lapatinib (yellow) by encasing the drug in an envelope of albumin (blue). Light from a near-infrared laser (center) was used to remotely trigger the release of the drug (right) after the nano-shells were taken up by cancer cells. Credit: A. Goodman/Rice University

Researchers investigating ways to deliver high doses of cancer-killing drugs inside tumors have shown they can use a laser and light-activated gold nanoparticles to remotely trigger the release of approved cancer drugs inside cancer cells in laboratory cultures.

The study by researchers at Rice University and Northwestern University Feinberg School of Medicine appears in this week’s online Early Edition of the Proceedings of the National Academy of Sciences. It employed gold nanoshells to deliver toxic doses of two drugs — lapatinib and docetaxel — inside breast cancer cells. The researchers showed they could use a laser to remotely trigger the particles to release the drugs after they entered the cells.

Though the tests were conducted with cell cultures in a lab, the research was designed to demonstrate clinical applicability: The nanoparticles are nontoxic, the drugs are widely used and the low-power, infrared laser can noninvasively shine through tissue and reach tumors several inches below the skin.

“In future studies, we plan to use a Trojan-horse strategy to get the drug-laden nanoshells inside tumors,” said Naomi Halas, an engineer, chemist and physicist at Rice University who invented gold nanoshells and has spent more than 15 years researching their anticancer potential. “Macrophages, a type of white blood cell that’s been shown to penetrate tumors, will carry the drug-particle complexes into tumors, and once there we use a laser to release the drugs.”

Co-author Susan Clare, a research associate professor of surgery at the Northwestern University Feinberg School of Medicine, said the PNAS study was designed to demonstrate the feasibility of the Trojan-horse approach. In addition to demonstrating that drugs could be released inside cancer cells, the study also showed that in macrophages, the drugs did not detach prior to triggering.

“Getting chemotherapeutic drugs to penetrate tumors is very challenging,” said Clare, also a Northwestern Medicine breast cancer surgeon. “Drugs tend to get pushed out of tumors rather than drawn in. To get an effective dose at the tumor, patients often have to take so much of the drug that nausea and other side effects become severe. Our hope is that the combination of macrophages and triggered drug-release will boost the effective dose of drugs within tumors so that patients can take less rather than more.”

If the approach works, Clare said, it could result in fewer side effects and potentially be used to treat many kinds of cancer. For example, one of the drugs in the study, lapatinib, is part of a broad class of chemotherapies called tyrosine kinase inhibitors that target specific proteins linked to different types of cancer. Other Federal Drug Administration-approved drugs in the class include imatinib (leukemia), gefitinib (breast, lung), erlotinib (lung, pancreatic), sunitinib (stomach, kidney) and sorafenib (liver, thyroid and kidney).

“All the tyrosine kinase inhibitors are notoriously insoluble in water,” said Amanda Goodman, a Rice alumna and lead author of the PNAS study. “As a drug class, they have poor bioavailability, which means that a relatively small proportion of the drug in each pill is actually killing cancer cells. If our method works for lapatinib and breast cancer, it may also work for the other drugs in the class.”

Halas invented nanoshells at Rice in the 1990s. About 20 times smaller than a red blood cell, they are made of a sphere of glass covered by a thin layer of gold. Nanoshells can be tuned to capture energy from specific wavelengths of light, including near-infrared (near-IR), a nonvisible wavelength that passes through most tissues in the body. Nanospectra Biosciences, a licensee of this technology, has performed several clinical trials over the past decade using nanoshells as photothermal agents that destroy tumors with infrared light.

Clare and Halas’ collaboration on nanoshell-based drug delivery began more than 10 years ago. In earlier work, they showed that a near-IR continuous-wave laser — the same kind that produces heat in the photothermal applications of nanoshells — could be used to trigger the release of drugs from nanoshells.

In the latest study, Goodman contrasted the use of continuous-wave laser triggering and triggering with a low-power pulse laser. Using each type of laser, she demonstrated the remotely triggered release of drugs from two types of nanoshell-drug conjugates. One type used a DNA linker and the drug docetaxel, and the other employed a coating of the blood protein albumin to trap and hold lapatinib. In each case, Goodman found she could trigger the release of the drug after the nanoshells were taken up inside cancer cells. She also found no measureable premature release of drugs in macrophages in either case.

Halas and Clare said they hope to begin animal tests of the technology soon and have an established mouse model that could be used for the testing.

“I’m particularly excited about the potential for lapatinib,” Clare said. “The first time I heard about Naomi’s work, I wondered if it might be the answer to delivering drugs into the anoxic (depleted of oxygen) interior of tumors where some of the most aggressive cancer cells lurk. As clinicians, we’re always looking for ways to keep cancer from coming back months or years later, and I am hopeful this can do that.”

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Materials provided by Rice UniversityNote: Content may be edited for style and length.

Northwestern University: The Power of the “Gene Chip” Coming to Nanotechnology: Ability to Rapidly Test Millions/ Billions of Nanoparticles at ONE Time

Nano Power Chip NW U 062316 id43777

A combinatorial library of polyelemental nanoparticles was developed using Dip-Pen Nanolithography. This novel nanoparticle library opens up a new field of nanocombinatorics for rapid screening of nanomaterials for a multitude of properties. (Image: Peng-Cheng Chen/James Hedrick)

The discovery power of the “gene chip” is coming to nanotechnology. A Northwestern University research team is developing a tool to rapidly test millions and perhaps even billions or more different nanoparticles at one time to zero in on the best particle for a specific use.

When materials are miniaturized, their properties — optical, structural, electrical, mechanical and chemical — change, offering new possibilities. But determining what nanoparticle size and composition are best for a given application, such as catalysts, biodiagnostic labels, pharmaceuticals and electronic devices, is a daunting task.
“As scientists, we’ve only just begun to investigate what materials can be made on the nanoscale,” said Northwestern’s Chad A. Mirkin, a world leader in nanotechnology research and its application, who led the study. “Screening a million potentially useful nanoparticles, for example, could take several lifetimes. Once optimized, our tool will enable researchers to pick the winner much faster than conventional methods. We have the ultimate discovery tool.”
Using a Northwestern technique that deposits materials on a surface, Mirkin and his team figured out how to make combinatorial libraries of nanoparticles in a very controlled way. (A combinatorial library is a collection of systematically varied structures encoded at specific sites on a surface.) Their study will be published June 24 by the journal Science.
Nano Power Chip NW U 062316 id43777The nanoparticle libraries are much like a gene chip, Mirkin says, where thousands of different spots of DNA are used to identify the presence of a disease or toxin. Thousands of reactions can be done simultaneously, providing results in just a few hours.


Similarly, Mirkin and his team’s libraries will enable scientists to rapidly make and screen millions to billions of nanoparticles of different compositions and sizes for desirable physical and chemical properties.

“The ability to make libraries of nanoparticles will open a new field of nanocombinatorics, where size — on a scale that matters — and composition become tunable parameters,” Mirkin said. “This is a powerful approach to discovery science.”
Mirkin is the George B. Rathmann Professor of Chemistry in the Weinberg College of Arts and Sciences and founding director of Northwestern’s International Institute for Nanotechnology.
“I liken our combinatorial nanopatterning approach to providing a broad palette of bold colors to an artist who previously had been working with a handful of dull and pale black, white and grey pastels,” said co-author Vinayak P. Dravid, the Abraham Harris Professor of Materials Science and Engineering in the McCormick School of Engineering.
Using five metallic elements — gold, silver, cobalt, copper and nickel — Mirkin and his team developed an array of unique structures by varying every elemental combination. In previous work, the researchers had shown that particle diameter also can be varied deliberately on the 1- to 100-nanometer length scale.
Some of the compositions can be found in nature, but more than half of them have never existed before on Earth. And when pictured using high-powered imaging techniques, the nanoparticles appear like an array of colorful Easter eggs, each compositional element contributing to the palette.
To build the combinatorial libraries, Mirkin and his team used Dip-Pen Nanolithography, a technique developed at Northwestern in 1999, to deposit onto a surface individual polymer “dots,” each loaded with different metal salts of interest. The researchers then heated the polymer dots, reducing the salts to metal atoms and forming a single nanoparticle. The size of the polymer dot can be varied to change the size of the final nanoparticle.
This control of both size and composition of nanoparticles is very important, Mirkin stressed. Having demonstrated control, the researchers used the tool to systematically generate a library of 31 nanostructures using the five different metals.
To help analyze the complex elemental compositions and size/shape of the nanoparticles down to the sub-nanometer scale, the team turned to Dravid, Mirkin’s longtime friend and collaborator. Dravid, founding director of Northwestern’s NUANCE Center, contributed his expertise and the advanced electron microscopes of NUANCE to spatially map the compositional trajectories of the combinatorial nanoparticles.
Now, scientists can begin to study these nanoparticles as well as build other useful combinatorial libraries consisting of billions of structures that subtly differ in size and composition. These structures may become the next materials that power fuel cells, efficiently harvest solar energy and convert it into useful fuels, and catalyze reactions that take low-value feedstocks from the petroleum industry and turn them into high-value products useful in the chemical and pharmaceutical industries.
Source: Northwestern University


Printing 3-D graphene structures for tissue engineering

graphene Nose -grain-bounderyEver since single-layer graphene burst onto the science scene in 2004, the possibilities for the promising material have seemed nearly endless. With its high electrical conductivity, ability to store energy, and ultra-strong and lightweight structure, graphene has potential for many applications in electronics, energy, the environment, and even medicine.

Now a team of Northwestern University researchers has found a way to print three-dimensional structures with graphene nanoflakes. The fast and efficient method could open up new opportunities for using graphene printed scaffolds regenerative engineering and other electronic or medical applications.

Led by Ramille Shah, assistant professor of materials science and engineering at Northwestern’s McCormick School of Engineering and of surgery in the Feinberg School of Medicine, and her postdoctoral fellow Adam Jakus, the team developed a novel graphene-based ink that can be used to print large, robust 3-D structures.

“People have tried to print graphene before,” Shah said. “But it’s been a mostly polymer composite with graphene making up less than 20 percent of the volume.”

With a volume so meager, those inks are unable to maintain many of graphene’s celebrated properties. But adding higher volumes of graphene flakes to the mix in these ink systems typically results in printed structures too brittle and fragile to manipulate. Shah’s ink is the best of both worlds. At 60-70 percent graphene, it preserves the material’s unique properties, including its electrical conductivity. And it’s flexible and robust enough to print robust macroscopic structures. The ink’s secret lies in its formulation: the graphene flakes are mixed with a biocompatible elastomer and quickly evaporating solvents.

“It’s a liquid ink,” Shah explained. “After the ink is extruded, one of the solvents in the system evaporates right away, causing the structure to solidify nearly instantly. The presence of the other solvents and the interaction with the specific polymer binder chosen also has a significant contribution to its resulting flexibility and properties. Because it holds its shape, we are able to build larger, well-defined objects.”

Supported by a Google Gift and a McCormick Research Catalyst Award, the research is described in the paper “Three-dimensional printing of high-content graphene scaffolds for electronic and biomedical applications,” published in the April 2015 issue of ACS Nano. Jakus is the paper’s first author. Mark Hersam, the Bette and Neison Harris Chair in Teaching Excellence, professor of materials science and engineering at McCormick, served as coauthor.

An expert in biomaterials, Shah said 3-D printed graphene scaffolds could play a role in tissue engineering and regenerative medicine as well as in electronic devices. Her team populated one of the scaffolds with stem cells to surprising results. Not only did the cells survive, they divided, proliferated, and morphed into neuron-like cells.

“That’s without any additional growth factors or signaling that people usually have to use to induce differentiation into neuron-like cells,” Shah said. “If we could just use a material without needing to incorporate other more expensive or complex agents, that would be ideal.”

The printed graphene structure is also flexible and strong enough to be easily sutured to existing tissues, so it could be used for biodegradable sensors and medical implants. Shah said the biocompatible elastomer and graphene’s electrical conductivity most likely contributed to the scaffold’s biological success.

“Cells conduct electricity inherently — especially neurons,” Shah said. “So if they’re on a substrate that can help conduct that signal, they’re able to communicate over wider distances.”

The graphene-based ink directly follows work that Shah and her graduate student Alexandra Rutz completed earlier in the year to develop more cell-compatible, water-based, printable gels. As chronicled in a paper published in the January 2015 issue of Advanced Materials, Shah’s team developed 30 printable bioink formulations, all of which are compatible materials for tissues and organs. These inks can print 3-D structures that could potentially act as the starting point for more complex organs.

“There are many different tissue types, so we need many types of inks,” Shah said. “We’ve expanded that biomaterial tool box to be able to optimize more mimetic engineered tissue constructs using 3-D printing.”

Story Source:

The above story is based on materials provided by Northwestern University. Note: Materials may be edited for content and length.

Journal Reference:

  1. Adam E. Jakus, Ethan B. Secor, Alexandra L. Rutz, Sumanas W. Jordan, Mark C. Hersam, Ramille N. Shah. Three-Dimensional Printing of High-Content Graphene Scaffolds for Electronic and Biomedical Applications. ACS Nano, 2015; 9 (4): 4636 DOI: 10.1021/acsnano.5b01179

Northwestern University: New Non-invasive Method Detects Alzheimer’s Disease Early

Alz new-non-invasive-method-can-detect-alzheimers-disease-early-tn-headerNo methods currently exist for the early detection of Alzheimer’s disease, which affects one out of nine people over the age of 65. Now, an interdisciplinary team of Northwestern University scientists and engineers has developed a noninvasive MRI approach that can detect the disease in a living animal. And it can do so at the earliest stages of the disease, well before typical Alzheimer’s symptoms appear.

Led by neuroscientist William L. Klein and materials scientist Vinayak P. Dravid, the research team developed an MRI (magnetic resonance imaging) probe that pairs a magnetic nanostructure (MNS) with an antibody that seeks out the amyloid beta brain toxins responsible for onset of the disease. The accumulated toxins, because of the associated magnetic nanostructures, show up as dark areas in MRI scans of the brain.
Alz new-non-invasive-method-can-detect-alzheimers-disease-early-tn-header
Fluorescent amyloid beta oligomers (green), bound to cultured hippocampal neurons, were detected with greater than 90 percent accuracy by the magnetic nanostructure probe (red). (Adapted from Viola et al., Nature Nanotechnology, 2014.)
This ability to detect the molecular toxins may one day enable scientists to both spot trouble early and better design drugs or therapies to combat and monitor the disease. And, while not the focus of the study, early evidence suggests the MRI probe improves memory, too, by binding to the toxins to render them “handcuffed” to do further damage.
“We have a new brain imaging method that can detect the toxin that leads to Alzheimer’s disease,” said Klein, who first identified the amyloid beta oligomer in 1998. He is a professor of neurobiology in the Weinberg College of Arts and Sciences.
“Using MRI, we can see the toxins attached to neurons in the brain,” Klein said. “We expect to use this tool to detect this disease early and to help identify drugs that can effectively eliminate the toxin and improve health.”
With the successful demonstration of the MRI probe, Northwestern researchers now have established the molecular basis for the cause, detection by non-invasive MR imaging and treatment of Alzheimer’s disease. Dravid introduced this magnetic nanostructure MRI contrast enhancement approach for Alzheimer’s following his earlier work utilizing MNS as smart nanotechnology carriers for targeted cancer diagnostics and therapy. (A MNS is typically 10 to 15 nanometers in diameter; one nanometer is one billionth of a meter.)
Details of the new Alzheimer’s disease diagnostic are published today (Dec. 22) by the journal Nature Nanotechnology. Klein and Dravid are co-corresponding authors.
The emotional and economic impacts of Alzheimer’s disease are devastating. This year, the direct cost of the disease in the United States is more than $200 billion, according to the Alzheimer’s Association’s “2014 Alzheimer’s Disease Facts and Figures.” By the year 2050, that cost is expected to be $1.1 trillion as baby boomers age. And these figures do not account for the lost time of caregivers.
This new MRI probe technology is detecting something different from conventional technology: toxic amyloid beta oligomers instead of plaques, which occur at a stage of Alzheimer’s when therapeutic intervention would be very late. Amyloid beta oligomers now are widely believed to be the culprit in the onset of Alzheimer’s disease and subsequent memory loss.
In a diseased brain, the mobile amyloid beta oligomers attack the synapses of neurons, destroying memory and ultimately resulting in neuron death. As time progresses, the amyloid beta builds up and starts to stick together, forming the amyloid plaques that current probes target. Oligomers may appear more than a decade before plaques are detected.
“Non-invasive imaging by MRI of amyloid beta oligomers is a giant step forward towards diagnosis of this debilitating disease in its earliest form,” said Dravid, the Abraham Harris Professor of Materials Science and Engineering at the McCormick School of Engineering and Applied Science.
There is a major need for what the Northwestern research team is doing — identifying and detecting the correct biomarker for new drug discovery. Despite extraordinary efforts, no effective drugs exist yet for Alzheimer’s disease.
“This MRI method could be used to determine how well a new drug is working,” Dravid said. “If a drug is effective, you would expect the amyloid beta signal to go down.”
The nontoxic MRI probe was delivered intranasally to mouse models with Alzheimer’s disease and control animals without the disease. In animals with Alzheimer’s, the toxins’ presence can be seen clearly in the hippocampus in MRI scans of the brain. No dark areas, however, were seen in the hippocampus of the control group.
The ability to detect amyloid beta oligomers, Klein said, is important for two reasons:  amyloid beta oligomers are the toxins that damage neurons, and the oligomers are the first sign of trouble in the disease process, appearing before any other pathology.
Klein, Dravid and their colleagues also observed that the behavior of animals with Alzheimer’s improved even after receiving a single dose of the MRI probe.
“While preliminary, the data suggests the probe could be used not only as a diagnostic tool but also as a therapeutic,” said Kirsten L. Viola, a co-first author of the study and a research manager in Klein’s laboratory.
Along with the studies in live animals, the research team also studied human brain tissue from Northwestern’s Cognitive Neurology and Alzheimer’s Disease Center. The samples were from individuals who died from Alzheimer’s and those who did not have the disease. After introducing the MRI probe, the researchers saw large dark areas in the Alzheimer brains, indicating the presence of amyloid beta oligomers.

Terahertz device could strengthen security

Northwestern_University_Seal_svgWe are all familiar with the hassles that accompany air travel. We shuffle through long lines, remove our shoes, and carry liquids in regulation-sized tubes. And even after all the effort, we still wonder if these procedures are making us any safer. Now a new type of security detection that uses terahertz radiation is looking to prove its promise. Able to detect explosives, chemical agents, and dangerous biological substances from safe distances, devices using terahertz waves could make public spaces more secure than ever.

But current terahertz sources are large, multi-component systems that sometimes require complex vacuum systems, external pump lasers and even cryogenic cooling. The unwieldy devices are heavy, expensive, and hard to transport, operate and maintain.

“A single-component solution capable of room temperature and widely tunable operation is highly desirable to enable next-generation terahertz systems,” said Manijeh Razeghi, Walter P. Murphy Professor of Electrical Engineering and Computer Science at Northwestern Univ.’s McCormick School of Engineering and Applied Science.

Director of Northwestern’s Center for Quantum Devices, Razeghi and her team have been working to develop such a device. In a recent paper in Applied Physics Letters, they demonstrate a room temperature, highly tunable, high-power terahertz source. Based on nonlinear mixing in quantum cascade lasers, the source can emit up to 1.9 mW of power and has a wide frequency coverage of 1 to 4.6 terahertz. By designing a multi-section, sampled-grating distribution feedback and distributed Bragg reflector waveguide, Razeghi and her team were also able to give the device a tuning range of 2.6 to 4.2 terahertz at room temperature.

The device has applications in medical and deep space imaging as well as security screening.

“I am very excited about these results,” Razeghi said. “No one would believe any of this was possible, even a couple years ago.”

Source: Northwestern Univ.

New process isolates promising material

graphene-structureAfter graphene was first produced in the laboratory in 2004, thousands of laboratories began developing graphene products worldwide. Researchers were amazed by its lightweight and ultra-strong properties. Ten years later, scientists now search for other materials that have the same level of potential.

“We continue to work with graphene, and there are some applications where it works very well,” said Mark Hersam, the Bette and Neison Harris Chair in Teaching Excellence at McCormick, who is a graphene expert. “But it’s not the answer to all the world’s problems.”

Part of a family of materials called transition metal dichalcogenides, molybdenum disulfide (MoS2) has emerged as a frontrunner material for exploration in Hersam’s laboratory. Like graphene, it can be exfoliated into atomically thin sheets. As it thins to the atomic limit, it becomes fluorescent, making it useful for optoelectronics, such as light-emitting diodes, or light-absorbing devices, such as solar cells. MoS2 is also a true semiconductor, making it an excellent candidate for electronics, and it historically has been used in catalysis to remove sulfur from crude oil, which prevents acid rain.

Hersam’s challenge was to find a way to isolate atomically thin sheets of this promising material at a larger scale. For the past six years, his laboratory has developed methods for exfoliating thin layers of graphene from graphite, using solution-based methods.

“You would think it would be easy to do the same thing for molybdenum disulfide,” he said. “But the problem is that while the exfoliation is similar to graphene, the separation is considerably more challenging.”

Hersam’s research is described in Nature Communications.

To sort graphene layers, Hersam used centrifugal force to separate materials by density. To do this, he and his group added the material to a centrifuge tube along with a gradient of water-based solution. Upon centrifugation, the denser species move toward the bottom, creating layers of densities within the centrifuge tube. Graphene sorts into single layer sheets toward the top, then bilayer sheets, trilayer and so on. Because graphene has a relatively low density, it easily sorts compared to higher density materials.

“If I use the exact same process with molybdenum disulfide, its higher density will cause it to crash out,” Hersam said. “It exceeds the maximum density of the gradient, which required an innovative solution.”

Hersam needed to take the inherently dense material and effectively reduce its density without changing the material itself. He realized that this goal could be achieved by tuning the density of the molecules used to disperse MoS2. In particular, the use of bulkier polymer dispersants allowed the effective density of MoS2 to be reduced into the range of the density gradient. In this manner, the sheets of MoS2 floated at layered positions instead of collecting as the bottom of the centrifuge tube. This technique works not just for MoS2, but for other materials in the transition metal dichalcogenides family.

“Now we can isolate single layer, bilayer, or trilayer transition metal dichalcogenides in a scalable manner,” Hersam said. “This process will allow us to explore their utility in large-scale applications, such as electronics, optoelectronics, catalysis, and solar cells.”

Source: Northwestern Univ.

Self-Assembled Membranes Hint at Biomedical Applications

1-SelfAssemblyAPS1Techniques for creating complex nanostructured materials through self-assembly of molecules have grown increasingly sophisticated. But carrying these techniques to the biological realm has been problematic. Recently, scientists from Northwestern University used self-assembly under controlled conditions to create a membrane consisting of layers with distinctly different structures. Now, working at the U.S. Department of Energy’s Advanced Photon Source (APS), the team utilized small-angle x-ray scattering (SAXS) to better determine these structures and study how they form. This new information paves the way for design and synthesis of hierarchical structures with biomedical applications.

Peptide amphiphiles (PA) are chains of amino acids tipped with other molecules so that one end is hydrophilic (mixes well with water) and the other hydrophobic (not fond of water). In aqueous solution, PAs form long, thin nanofibers as the amino acid chains bind to adjacent chains to form β–sheets. The Northwestern University scientists had previously found that when an aqueous solution containing positively-charged PAs was put into contact with an aqueous solution of negatively charged hyaluronic acid (HA—a large biological molecule that occurs in connective and other tissues), a dense, fibrous layer formed within milliseconds, creating a barrier that kept the two solutions from mixing.


More precisely, the researchers found that the fibrous layer prevents aggregated PAs from migrating to the HA side, but allows HA molecules to slowly insinuate themselves through the barrier to the PA side, on a timescale of minutes or longer.

The result was a three-zone membrane structure: a gel-like layer on the HA side, a fibrous mat consisting of PA nanofibers lying in the plane of the interface between the solutions, and a coating of fibers directed perpendicularly away from the interface and formed by electrostatically bound complexes of PA and HA (Image 1).

The team’s interest in these membranes hinged on possible biomedical uses in which the peptide sequence forming the nanofibers would have a chosen biological activity. In one example, they incorporated a heparin-binding sequence to promote angiogenesis (the formation of new blood vessels), so that the membrane might assist with tissue repair. For the three-zone structure to form, the researchers found that the HA solution had to contain heparin in a certain concentration range. Scanning electron microscopy clearly showed linear structure crossing the membrane that formed when heparin was present at 0.5% by weight (Image 2a), in contrast to the more homogeneous appearance of the membrane created in the absence of heparin (Image 2b).

Scanning electron micrographs show the homogeneous membrane that forms in the absence of heparin (A), while in the presence of heparin is a fibrous structure forms transverse to the membrane (B).Scanning electron micrographs show the homogeneous membrane that forms in the absence of heparin (A), while in the presence of heparin is a fibrous structure forms transverse to the membrane (B).The scientists turned to SAXS at the DuPont-Northwestern-Dow Collaborative Access Team beamline 5-ID-D at the Argonne APS, an Office of Science user facility. These studies yield insight into the precise structure of the three-zone membranes and a better understanding of the dynamics of their formation.

The heparin-free membranes produced well-defined Bragg peaks, while the three-zone membranes did not. Moreover, membranes that arose in the presence of smaller heparin concentrations showed larger Bragg peaks than those produced when the heparin concentration was higher, indicating a competition between two structures whose outcome depended on heparin levels.

A time-series of SAXS measurements on a heparin-free experiment showed that the Bragg peaks began to form a few minutes after the two solutions were brought into contact, and reached full strength after about 45 minutes.

Interpreting the SAXS findings in the light of their previous experiments and the known properties of PAs and HA, the scientists explain the differences between the two types of membrane as the result of different kinds of aggregation. In the absence of heparin, the PA and HA come together in nanospherical aggregates that pack together in a cubic arrangement, over a period of some tens of minutes, to form a membrane that generates well-defined Bragg peaks.

When heparin is present, by contrast, it binds strongly with the PA and alters its interaction with AH molecules. In this case, a barrier of nanofibers lying parallel to the solution interface forms immediately, then acts as a diffusion barrier through which HA slowly passes. As it emerges on the other side, it binds to PA to form nanofibers that grow perpendicular to the interface. This ordered nanofiber array produces no Bragg peaks.

The increased understanding and control of these processes derived from this research could make it possible to build bioactive membranes with a variety of structures and purposes.

Electrostatic Control of Structure in Self-Assembled Membranes

Source: Argonne National Laboratory