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Wednesday, August 6th, 2014

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    12:00a
    New material structures bend like microscopic hair

    MIT engineers have fabricated a new elastic material coated with microscopic, hairlike structures that tilt in response to a magnetic field. Depending on the field’s orientation, the microhairs can tilt to form a path through which fluid can flow; the material can even direct water upward, against gravity.

    Each microhair, made of nickel, is about 70 microns high and 25 microns wide — about one-fourth the diameter of a human hair. The researchers fabricated an array of the microhairs onto an elastic, transparent layer of silicone.

    In experiments, the magnetically activated material directed not just the flow of fluid, but also light — much as window blinds tilt to filter the sun. Researchers say the work could lead to waterproofing and anti-glare applications, such as “smart windows” for buildings and cars.

    “You could coat this on your car windshield to manipulate rain or sunlight,” says Yangying Zhu, a graduate student in MIT’s Department of Mechanical Engineering. “So you could filter how much solar radiation you want coming in, and also shed raindrops. This is an opportunity for the future.”

    In the near term, the material could also be embedded in lab-on-a-chip devices to magnetically direct the flow of cells and other biological material through a diagnostic chip’s microchannels.

    Zhu reports the details of the material this month in the journal Advanced Materials. The paper’s co-authors are Evelyn Wang, an associate professor of mechanical engineering, former graduate student Rong Xiao, and postdoc Dion Antao.

    Nature’s dynamics

    The inspiration for the microhair array comes partly from nature, Zhu says. For example, human nasal passages are lined with cilia — small hairs that sway back and forth to remove dust and other foreign particles. Zhu sought to engineer a dynamic, responsive material that mimics the motion of cilia.

    “We see these dynamic structures a lot in nature,” Zhu says. “So we thought, ‘What if we could engineer microstructures, and make them dynamic?’ This would expand the functionality of surfaces.”

    Zhu chose to work with materials that move in response to a magnetic field. Others have designed such magnetically actuated materials by infusing polymers with magnetic particles. However, Wang says it’s difficult to control the distribution — and therefore the movement — of particles through a polymer.

    Instead, she and Zhu chose to manufacture an array of microscopic pillars that uniformly tilt in response to a magnetic field. To do so, they first created molds, which they electroplated with nickel. They then stripped the molds away, and bonded the nickel pillars to a soft, transparent layer of silicone. The researchers exposed the material to an external magnetic field, placing it between two large magnets, and found they were able to control the angle and direction of the pillars, which tilted toward the angle of the magnetic field.

    “We can apply the field in any direction, and the pillars will follow the field, in real time,” Zhu says.

    Tilting toward a field

    In experiments, the team piped a water solution through a syringe and onto the microhair array. Under a magnetic field, the liquid only flowed in the direction in which the pillars tilted, while being highly “pinned,” or fixed, in all other directions — an effect that was even seen when the researchers stood the array against a wall: Through a combination of surface tension and tilting pillars, water climbed up the array, following the direction of the pillars.

    Since the material’s underlying silicone layer is transparent, the group also explored the array’s effect on light. Zhu shone a laser through the material while tilting the pillars at various angles, and found she could control how much light passed through, based on the angle at which the pillars bent.

    In principle, she says, more complex magnetic fields could be designed to create intricate tilting patterns throughout an array. Such patterns may be useful in directing cells through a microchip’s channels, or wicking moisture from a windshield. Since the material is flexible, Wang says that it may even be woven into fabric to create rain-resistant clothing.

    “A nice thing about this substrate is that you can attach it to something with interesting contours,” Wang says. “Or, depending on how you design the magnetic field, you could get the pillars to close in like a flower. You could do a lot of things with the same platform.”

    This research was supported by funding from the Air Force Office of Scientific Research.

    12:59p
    A new way to model cancer

    Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer. One way to discover the role of these mutations is to breed a strain of mice that carry the genetic flaw — but breeding such mice is an expensive, time-consuming process.

    Now, MIT researchers have found an alternative: They have shown that a gene-editing system called CRISPR can introduce cancer-causing mutations into the livers of adult mice, enabling scientists to screen these mutations much more quickly.

    In a study appearing in the Aug. 6 issue of Nature, the researchers generated liver tumors in adult mice by disrupting the tumor suppressor genes p53 and pten. They are now working on ways to deliver the necessary CRISPR components to other organs, allowing them to investigate mutations found in other types of cancer.

    “The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations. The flexibility of this technology, as delivery gets better in the future, will give you a way to pretty rapidly test those combinations,” says Institute Professor Phillip Sharp, an author of the paper.

    Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology, is the paper’s senior author. The lead authors are Koch Institute postdocs Wen Xue, Sidi Chen, and Hao Yin.

    Gene disruption

    CRISPR relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this bacterial system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.

    In some cases, the researchers simply snip out part of a gene to disrupt its function; in others, they also introduce a DNA template strand that encodes a new sequence to replace the deleted DNA.

    To investigate the potential usefulness of CRISPR for creating mouse models of cancer, the researchers first used it to knock out p53 and pten, which protect cells from becoming cancerous by regulating cell growth. Previous studies have shown that genetically engineered mice with mutations in both of those genes will develop cancer within a few months.

    Studies of such genetically engineered mice have yielded many important discoveries, but the process, which requires introducing mutations into embryonic stem cells, can take more than a year and costs hundreds of thousands of dollars. “It’s a very long process, and the more genes you’re working with, the longer and more complicated it becomes,” Jacks says.

    Using Cas enzymes targeted to cut snippets of p53 and pten, the researchers were able to disrupt those two genes in about 3 percent of liver cells, enough to produce liver tumors within three months.

    Many models possible

    The researchers also used CRISPR to create a mouse model with an oncogene called beta catenin, which makes cells more likely to become cancerous if additional mutations occur later on. To create this model, the researchers had to cut out the normal version of the gene and replace it with an overactive form, which was successful in about 0.5 percent of hepatocytes (the cells that make up most of the liver).

    The ability to not only delete genes, but also to replace them with altered versions “really opens up all sorts of new possibilities when you think about the kinds of genes that you would want to mutate in the future,” Jacks says. “Both loss of function and gain of function are possible.”

    Using CRISPR to generate tumors should allow scientists to more rapidly study how different genetic mutations interact to produce cancers, as well as the effects of potential drugs on tumors with a specific genetic profile.

    “This is a game-changer for the production of engineered strains of human cancer,” says Ronald DePinho, director of the University of Texas MD Anderson Cancer Center, who was not part of the research team. “CRISPR/Cas9 offers the ability to totally ablate gene function in adult mice. Enhanced potential of this powerful technology will be realized with improved delivery methods, the testing of CRISPR/Cas9 efficiency in other organs and tissues, and the use of CRISPR/Cas9 in tumor-prone backgrounds.”

    In this study, the researchers delivered the genes necessary for CRISPR through injections into veins in the tails of the mice. While this is an effective way to get genetic material to the liver, it would not work for other organs of interest. However, nanoparticles and other delivery methods now being developed for DNA and RNA could prove more effective in targeting other organs, Sharp says.

    The research was funded by the National Institutes of Health and the National Cancer Institute.

    4:31p
    Undersea living: Alumna joins Cousteau mission

    What’s it like living on the bottom of the ocean in a habitat no bigger than a school bus for more than two weeks? Nicer than you might think, according to Grace Young ’14.

    “It was comfortable. I felt like I could have a vacation house underwater,” the mechanical and ocean engineering alumna says of her stint with Fabien Cousteau’s "Mission 31."

    In her blog, "Grace Under Pressure," Young described her 15 days in Florida International University’s Aquarius habitat as an aquanaut with Mission 31. The mission’s purpose was to raise awareness of climate change, ocean pollution, and overconsumption of resources while facilitating experiments and research unique to the underwater marine laboratory.

    Young and her fellow aquanauts spent their days in saturation diving — a style of diving that allows for multiple hours of submersion, due to living in a pressurized environment like Aquarius — and assisting with research.

    Extended dive times and the established habitat — Aquarius has been in the same location for 21 years — allowed for distinctive experiences.

    “Fish would come up to the window and look us in the eye. You start to feel like you’re part of the ocean,” Young says. “It gives you a chance for really great research and incredible footage.”

    While diving, Young led the team in using the Edgertronic, a high-speed video camera created by Mike Matter ’84, to film coral, plants, moving fins, and feeding mantis shrimp. “These are things that have never been filmed in slow-motion in the wild before,” she explains.

    Besides assisting with others’ research projects, Young performed her own work on the goliath grouper, an enormous fish whose feeding habits intrigued her.

    “On my last dive, there was a school of fish with grouper snapping away at them. You can feel the grouper as they open their mouths, it creates a mini sonic boom,” she says.

    Young says it’s too early to discuss the results of the many research projects, but expects some exciting results. “Some of the more surprising results will come from the environmental contamination sensors we put out and the zooplankton samples we collected at different times of day,” she says.

    Young was originally invited to join the mission early last year, but delays pushed the mission date to June, causing her to miss MIT's Commencement. “It was a no brainer,” Young says of her decision to flip her "Brass Rat" — MIT's class ring — underwater, thousands of miles from Killian Court.

    Young, a Marshall Scholar, is moving on to Oxford University in the fall to pursue a PhD in offshore engineering. She says she’s grateful for MIT, the first place she was able to combine two loves into a degree.

    “My love for the ocean was separate from my love for engineering until I got to MIT,” she says.

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