14 Undergraduate Interns Gain Experience in MIT Labs
Synthesizing thin films for rechargeable batteries, exploring catalysts for the oxygen evolution reaction needed in fuel cells and testing origami-inspired self-folding materials were among the projects tackled by 14 MPC and CMSE Summer Scholars.
- 2014 MPC-CMSE Summer Scholars 2014 MPC-CMSE Summer Scholars
- Alyssa Johnson Alyssa Johnson
- Catherine Groschner Catherine Groschner
- Eric Bailey Eric Bailey
- Gabriel Denham Gabriel Denham
- Jessica Ma Jessica Ma
- John Lee John Lee
- Julia Zhao Julia Zhao
- Karen Diaz Karen Diaz
- Kayla Robinson Kayla Robinson
- Kevin Romero Kevin Romero
- Rahul Kini Rahul Kini
- Meredith Fields Meredith Fields
- Naomi Morales Naomi Morales
- Sarah Arveson Sarah Arveson
Meredith Fields built and tested self-folding hinges in origami-inspired laminates whose folding action is triggered by electricity. Fields worked in the lab of Professor A. John Hart, who also is examining self-folding triggered by blue LED light.
To study the mechanical behavior of laminate hinges, Fields created the laminates by laser cutting paper hinges, applying a pressure-sensitive adhesive and attaching a biaxially pre-strained polymer like PVC, or polyethylene, to the adhesive. The self-folding mechanism can be activated by electricity, heat or light.
“I’m testing an electrically actuated system, in which I flow current through conductive carbon, and when I do that, it heats the conductive carbon and through conduction heats the hinge. Since it’s a heat sensitive polymer it will shrink and create a fold, so this is the basis of self-folding hinges,” Fields says. The millimeter to centimeter scale laminates have a potential to be used in batteries.
“Meredith will have the experience of preparing a conference presentation and she’s been doing some other great work on mechanical design,” graduate student Abhinav Rao says. Fields contributed to a presentation by Hart for the 6th International Meeting of Origami Science, Mathematics and Education (OSME) conference in Japan in August 2014.
Rahul Kini experimented with building thin film batteries in the lab of Professor Carl V. Thompson. The micro batteries are built up over several hours in an electron sputtering machine, depositing onto a silicon wafer substrate layers of current collector anodes and cathodes (usually titanium or platinum), silicon for the anode, lithium phosphorus oxynitride (LiPON) for the electrolyte, lithium cobalt oxide for the cathode and a coating of titanium to prevent the LiPON from reacting with oxygen in air. The material is about 1 micron, or 1,000 nanometers, thick.
“What we’re really trying to achieve is high energy density, high energy capacity and reusability,” Kini says. “If you have a lot of energy that’s great, but if it’s reusable it’s even better. What we’re trying to see is can we reuse this for 50 cycles, 100 cycles…. If we can stack all these thin films, then we are going to have a huge energy capacity, a huge voltage. What we’re really looking at is reliability over the long term.” Related video.
Exploring Solar Alternatives
Sarah Arveson studied methyl ammonium lead bromide thin films in the lab of Professor William Tisdale. She experimented with different thin film synthesis techniques, varying thickness and temperature, comparing spin coating versus drop casting, and working in a nitrogen-filled glove box. Spin coating at 1,500 rotations per minute causes the solvent to evaporate more quickly and produces thin, uniform films. She also made scanning electron microscope images of the perovskite films, which form into cubic crystals at room temperature and pressure, and saw a mix of cubic and tetragonal phases. The tetragonal phase is more stretched in one direction.
Arveson also experimented with hybrid films doped with iodine. “Instead of three bromine molecules, there will be two iodine or one iodine,” she explains. The iodine could cause different optical or structural properties in the crystal. The methyl ammonium lead bromide thin films with their perovskite crystal structure show potential for high-efficiency solar cells. “They’re inorganic-organic hybrid molecules, so the inorganic gives you very high charge carrier mobility, while the organic part gives you malleability. It’s very soft and flexible,” Arveson explains. Related video.
Forming Hollow Fibers
Karen Diaz Toledo, working under Professor Yoel Fink, made thin films from polycaprolactone polymer pellets, winding several layers around a hollow rod to a diameter of about 30 millimeters. The rolls are drawn into hollow fibers and could be used for drug delivery or cell transport.
Attaching Quantum Dots
John Lee, working with graduate student Noémie-Manuelle Dorval Courchesne in the lab of Professor Paula Hammond, studied the use of virus-based quantum dot nanowires for solar cell applications. Lead sulfide (PbS) quantum dots are dissolved in water, where they are attached to bacteriophages. "We're trying to make quantum dots that are positively charged because the bacteriophage is negatively charged, and we want to assemble them with electrostatic interaction," Courchesne explains.
"I've been learning a lot because I don't have much background in these type of ligand exchange studies," Lee says. "In order to make this happen, you have to be very knowledgeable in how ligands work. We are trying to use the (bacterio)phages and the quantum dots, so we can hopefully see a improvement in the efficiency of the solar cell."
Fighting Canister Corrosion
Jessica Ma undertook the study of corrosion in nuclear fuel canisters under Professor Ron Ballinger. She used a coordinate measurement machine to map the surface of a sample block at 3,000 different points to provide a baseline for comparison in corrosion studies of nuclear fuel canisters. Ma studied stress analysis of the nuclear canisters and helped to create a model for calculating residual stress on the surface.
Understanding Oxide Catalysis
Working under Professor Yang Shao-Horn, Alyssa Johnson explored how to catalyze the oxygen evolution reaction in various oxide films, measuring the applied potential to electrodes for 20 different oxides, including lanthanum strontium cobalt oxide. Johnson worked with carbon electrodes, processing them in measuring resistance with rotating disc electroanalysis. "We're looking at the materials for fuel cell applications," Johnson says.
The process begins with making an ink that combines the oxide powder with carbon and applying it to the electrode so it will bind well to the surface. "Once I bind it with certain chemicals, I can deposit it onto the surface of the electrode," she explains. The electrode is then heated in the furnace for a minute and dropped into potassium hydroxide electrolyte for analysis.
"We're going to look at a cyclic voltammetry chart to see what happens when we apply a potential. That will tell us how good these materials are for the oxygen evolution reaction," Johnson says.
Probing Carbon Nanocomposites
Naomi Morales Medina used an X-ray diffraction system to analyze the structure of nanocomposite carbon materials and search for defects. Such materials are fabricated in industry for aeronautics and defense. Morales worked under Professor Brian Wardle.
The material, comprised of phenolic resin and carbon nanotubes, is heated to 1,000 degrees Celsius in the device and examined with X-rays to reveal its crystal structure. "With this in situ technique, I'm reaching temperatures of 600, 800, 1,000 degrees for my sample. The purpose of applying so much heat is just to know about the defects of the sample. Using this we have real nice results. This work will be eventually for publication," Morales says.
Seeking Graphene Bandgap
Gabriel Denham undertook a computational analysis of adding an amide found in nature to graphene as a way to coax an electronic bandgap in graphene. Working under Professor Markus Buehler, Denham used density functional theory and molecular dynamics software to analyze the potential for applications in electronics.
"Both boron nitride and graphene are potential candidates for high-powered semiconductors that could potentially replace silicon, but ... graphene has no bandgap and boron nitride has too large a bandgap to be actually used for those applications right now," Denham says. "We're taking a bio-binder, which is a really fancy way of saying it's this molecule that's found in pig manure, so it's completely natural, and what we're interested in is particularly the amide portion of this bio-binder, that exhibits a really large delocalization of electrons. We're hoping that by putting it close to either graphene or boron nitride, we'll see some sort of electronic reaction between the two and either the creation of a bandgap in graphene or the reduction of the bandgap in boron nitride."
Controlling Hydrogel Defects
Julia Zhao worked with Postdoctoral Associate Mingjiang Zhong exploring defects in hydrogels with potential applications such as an extracellular matrix. "The basic idea is trying to quantify the primary loop reactions in relation to the mechanical properties of a gel (hydrogels)," Zhao says of the joint project under Professors Brad Olsen and Jeremiah Johnson.
"The challenge of this project is in most gels or elastomers you always end up with some primary loop, which is a defect in the gel," Zhong says. "The goal is to control the number of defects and also to improve mechanical properties."
Making Conductive Hydrogels
Eric Bailey synthesized composite hydrogel materials of carbon nanotubes embedded in a polymer, working in the lab of Professor Cullen Buie.
"We'd like it to be a network of carbon nanotubes, so that gives it conductivity" Bailey says. The hydrogels are about 10 microns thick.
Measuring Cartilage Changes
Kayla Robinson focused on high and low glucose concentrations and their effect on cartilage. Working under Professor Alan Grodzinsky, Robinson We conducted one experiment for eight days and another for 22 days. "The eight-day we have four conditions, high glucose, low glucose, then high glucose with IL 1 (interleukin-1beta protein) and low glucose with IL 1."
Studying changes in cartilage from the knee joint of cows, Robinson measured the release of glycoaminoglycan (GAG), a sugar-like molecule, released from the
Processing Carbon Dioxide
Catherine Groschner explored bimetallic catalysts for turning carbon dioxide into carbon monoxide for synthesis gas, which could then be transformed into transportation fuels. Working under Professor Fikile Brushett, Groschner used galvanic replacement reactions to modify copper foils and tested their effectiveness at carbon dioxide reduction.
Groschner studied the effect of varying the elemental composition and surface structure of copper foils via the addition of different ad-atoms with a goal of improving catalytic performance. "We're trying to make something here that's a lot of trial and error," Groschner says. "It's all brand new, I've never done any sort of electrochemistry before, and particularly not catalysis."
Catalyzing chemical intermediate
Kevin Romero evaluated water-based catalytic conditions to make a specific molecule that is an intermediate in production of certain pharmaceuticals and herbicides. Working under Professor Yuriy Roman, Romero says, "We have a couple of catalysts that we're testing, and we're testing different reaction conditions."
Romero looked at different amounts of water, with the different catalysts, to try to make the most efficient synthesis possible. After carefully measuring and mixing the chemical ingredients, Romero puts the solution in a metal reactor chamber. The air is flushed out of the chamber with an inert gas three times, then heated to 160 degrees Celsius at about 20 times the pressure of earth's atmosphere. "It's pretty high pressure, which is why the reactor is as intense as it looks," Romero says.
The Summer Scholars presented their research at a Poster Session Aug. 7, 2014.
Visiting graduate student studies high-throughput manufacturing of precisely shaped micro particles.
Ryan Oliver, a visiting graduate student of Associate Professor of Mechanical Engineering A. John Hart, is working on a technique called Maskless Fluidic Lithography that allows creation of unique shapes in a liquid polymer such as PEG-DA by exposing it to patterned ultraviolet light, a process known as photo-polymerization.
|Examples of micro shapes polymerized by ultraviolet light in polyethylene glycol diacrylate (PEG-DA). SEM image courtesy of Ryan Oliver, Mechanosynthesis Group.|
For example, working with a common biocompatible polymer, polyethylene glycol diacrylate (PEG-DA), Oliver uses a projector as a mask to pattern shapes. Unlike the wafer masks used in semiconductor processing, which are produced as single use items, the integrated projection system allows for rapid change of the pattern.
Key to the system is a Texas Instruments Digital Micromirror Device (DMD), which can be reconfigured easily by turning on and off micro mirrors to produce a multitude of shapes. The mirrors can turn on and off 32,552 times a second. “Because the mirrors are so fast, we can make decisions very quickly, which is hard to do with a masked system. You would spend several days ordering or fabricating a mask rather than milliseconds if you needed a new pattern," he says. For the polymer processing, the amount of 365-nanometer light being projected can be controlled by the mirrors. Because of the ability to control how long each mirror is switched on during a single second, the projection varies in intensity, which enables formation of two-dimensional or three-dimensional structures. Oliver likens the process to layer-by-layer assembly in a single step.
The stop flow lithography approach, inspired by research reported by Patrick Doyle's group at MIT, was chosen while Ryan and Professor Hart were at the University of Michigan as a platform for studying the manufacture of large quantities of custom micro-particles. The vision is to use particles that are designed to work together and act as a sensitive biosensor. To realize the vision, Ryan has a goal to produce micro particles from about 250nm to about 100 microns with a library of shapes such as diamonds, triangles, squares and octagons. "We're exploring methods of taking them down to the nano scale, but the current system produces micro particles," Oliver says.
Visiting graduate student Ryan Oliver with a microscope. Oliver's projects under Associate Professor of Mechanical Engineering A. John Hart include the Robofurnace, an automated system for making carbon nanotube forests and studying their growth, and high-throughput manufacturing of polymer microstructures for biosensing. Photo: Denis Paiste, Materials Processing Center
“The thing that sets this method apart is one, high throughput, two, flexibility using the DMD chip, and three, the fact that you can control the shape as well as the size of the particles, and possibly the chemistry,” Oliver explains.
Oliver is studying how to manipulate a collection of polymer particles on a liquid surface in order to assemble them in specific ways. “We needed a platform in order to synthesize micro particles that we could perform self-assembly experiments on because that promises to allow us to build sensors that we can’t build now, that are too complex; they’re made out of too many types of materials to fabricate using traditional manufacturing methods,” Oliver says. “A lot of applications may require control over the shape, the surface finish, the chemistry and the size of micro particles, so we’ve been exploring this as a method toward that end as well as understanding how to improve the shape accuracy while increasing throughput, so that's a future goal."
Oliver is a visiting graduate student under Associate Professor of Mechanical Engineering A. John Hart whom he followed to MIT from the University of Michigan. He also led work on the Robofurnace project, an automated bench top chemical vapor deposition system for growing carbon nanotubes and other nano materials. He hopes to finish his Ph.D. through Michigan in August 2013. His dissertation will focus on a suite of tools for high-throughput polymer micromanufacturing and manipulation, including the direct-write fluidic lithography method.
Oliver presented his work on polymers at a Materials Research Society meeting and the Enabling Nanofabrication for Rapid Innovation workshop in 2013 but hasn't published his results in a journal yet.
Such templates polymers can be used for a range of processes from drug delivery to cell culture assays to casting molds. Researchers in Professor Hart's Mechanosynthesis Lab also adapted the UV-light based polymerization to a roll-to-roll system in addition to the microfluidic system.
One drawback with PEG, which is a hydrogel, is it readily absorbs water, so it can
swell or change shape in wet environments.
"Beyond the manufacturing process, we are interested in secondary means to assemble the particles into complex, hierarchical structures, such as those including cells. These assemblies could be very useful for performing high-throughput bioassays or building novel tissue-like structures," Oliver says.
– Written by Denis Paiste, Materials Processing Center
Manipulating charges on molecules facilitates transport, MIT Post-Doc Leon Li demonstrates
The mucus barrier prevents passage of harmful germs wherever it covers delicate wet cells in the human body called epithelia, but it also poses a major obstacle for the delivery of drugs. One important question in the field is how to equip drug delivery vehicles so they manage to pass through the protective mucus barrier.
|Dr. Leon Li holds a microfluidic device used to test how effectively molecules called peptides can pass through a mucus barrier. Photo: Denis Paiste, Materials Processing Center|
Recent research by MIT postdoctoral associate Dr. Leon Li shows that ionic charges on molecules and the spatial arrangement of those charges each play a key role in transport through mucus.
Li created a microfluidic device that creates a tiny mucus barrier, mimicking the body's own. "Our microfluidic devices are designed to study animal and human mucus samples and experimentally mimic the geometry and physiology of the body's natural mucus barriers. We use these devices to perform detailed measurements of the interaction of molecules, viruses, and drug carriers with the mucus barriers. We also used these devices to study acid transport through mucus barriers. I realized that could be used to study protein transport and drug transport, so I adapted those devices," Li said. The Laboratory for Biological Hydrogels now has a suite of microfluidic tools designed and fabricated by Li in collaboration with Prof. Jongyoon Han's lab. The devices allow the researchers to reconstitute specific aspects of mucus transport that are much easier to measure outside the body.
To probe the fundamental criteria underlying the selective filtration properties of the mucus barriers, Li used microfluidics in conjunction with novel peptide based molecular probes.
Close up image of microfluidic device with U.S. quarter for comparison.Li used fluorescent microscopy, a well-established technique, to image and compare the differences in mucus penetration by differently configured peptides.
Four groups of peptides were tested: positively charged peptides, negatively charged peptides and peptides carrying a mix of negative and positive charges in two different arrangements.
"The mucus interacts with the peptides to change the transport of these peptides in very specific ways depending on what peptide it is and how the charge is distributed on that peptide," he said. By using isomers of a peptide – peptides consisting of the same number of atoms but with different spatial arrangements of their atoms and charges – Li and colleagues were able to show in the "Biophysical Journal" paper, "Spatial Configuration and Composition of Charge Modulates Transport into a Mucin Hydrogel Barrier," that spatial arrangements of ionic charge can affect transport.
Nanometer scale changes
|DR. LEON LI|
These changes can take place on a very small scale, on the order of nanometers, Li said. The peptides he studied are about 10 nanometers long. "When you make arrangement changes on the order of nanometers, you can modulate the transport behavior of molecules inside of mucus," he said.
The new findings point to a new tool for designing drug and gene carriers – specific surface charge configurations to optimize interactions with mucins in mucus for diseases such as cystic fibrosis and gastric ulcers. The paper's authors included Ribbeck, EECS Professor Jongyoon Han, MIT post-doctoral associate Thomas Crouzier (link to Crouzier article), electrical engineering graduate student Aniruddh Sarkar and biological engineering graduate student Laura Dunphy.
Drugs carriers have either been positively, negatively or neutrally charged and thought of as either adhesive or non-interactive. But Li's research opens a new set of possibilities based on nature itself to use spatial configuration on a very small scale as a selectivity criteria for transport across mucus barriers. "We are showing, in a sense, an additional finely tuned lever that lets us optimize how we send drugs across mucus barriers," Li said. The research also opens the possibility of engineering different materials or molecules that can improve mucus barrier function.
Strengthening the mucus barrier against chemical and biological agents might also be used for defense applications. The work did not consider hydrophobicity, which opens another line of inquiry for future work.
"Our contribution here is demonstrating that our very precise tools using peptides with very precise variations on charge – spatial variation of charge – can have profound effect on transport into mucus barriers." Li said.
Li, who enjoys hiking, cooking and socializing, hopes to work as research scientist or engineer in industry when he finishes his work as a post-doc at MIT.
MIT post-doc Thomas Crouzier discovers substitute that restores water-absorption
Dr. Thomas Crouzier, a postdoctoral associate at MIT's Laboratory for Biological Hydrogels, holds a sample of a gel reconstituted from mucins. Mucins are a key component of mucus, which MIT's Laboratory for Biological Hydrogels studies to learn how mucus functions and how to promote its recovery when it fails. Photo: Denis Paiste, Materials Processing Center
Mucus hydrates and lubricates the eyes, the nose and the digestive and urogenital tracts. It gets its slippery, wet qualities from mucins — biopolymers with a protein backbone encrusted with sugars. If mucins are scarce or compromised, health problems result, including dry eye, dry mouth, an increased susceptibility to microbial infections, and a compromised ability to absorb food.
But, just as there is no substitute for human blood, there are no good substitutes yet for mucin. MIT researchers are exploring how mucin works in hopes of eventually developing substitutes.
Thomas Crouzier, a postdoctoral fellow at MIT's Laboratory for Biological Hydrogels, recently demonstrated, through research on mucus from pig stomachs, that in mucin play a key role in its ability to absorb water and provide lubrication. And he discovered a way to restore these qualities to mucins stripped of their sugars. Working with Johnson & Johnson scientists and MIT colleagues, Crouzier showed that substituting polyethylene glycol chains for missing sugar molecules can partly restore mucin's water-absorbing capacity and lubricating potential.
This work is a starting point toward recovering loss of function in altered mucins, and designing fully synthetic mucins. Besides Crouzier, MIT professor Katharina Ribbeck, graduate student Nicole Kavanaugh, and Johnson & Johnson scientists Anthony R. Geonnotti and Julie B. Hirsch are co-authors of a manuscript that is in preparation.
The ability of mucin polymers to hold large amounts of water is critical to keeping our epithelial cells healthy. Understanding how mucins do this could lead to better treatments for when they fail.
As part of the research, Crouzier measured the amount of water that mucins could bind. "The mucins on the surface [of mucus] will absorb a lot of water; the coating that is formed on the surface is 90 percent water. Other proteins that I've tested here bind a lot less water," Crouzier says.
In friction tests, graduate student Nicole Kavanaugh and Johnson & Johnson scientists Anthony R. Geonnotti and Julie B. Hirsch found that a solution containing mucins is several orders of magnitude slipperier than a solution that just contains salts. "It shows you how very efficient this molecule is at lubricating surfaces," Crouzier says.
Crouzier studied the role of mucin-attached glycans (sugars) in water absorbency and lubrication because they make up from half to almost 90 percent of mucins' weight and are known to be highly water-absorbent. Crouzier's experiments showed that stripping the mucins of some or all of their attached sugars robs them of their sponge-like absorbency and their lubricating ability. "That tells us that the sugars are really important for both of these properties," he says.
Thomas Crouzier, top, holds a gold-coated quartz crystal microbalance which is used in a fluorescent microscope to measure the watery content of coatings on natural and modified pig gastric mucin. Below, close up of quartz crystal microbalance. Photos: Denis Paiste, Materials Processing Center
The sugars, which give mucins a brush-like extended structure, may also aid lubrication by keeping the protein backbone from rolling into a ball. "When you remove the sugars, they can fold and be more globular and collapsed, so there is less space to hold water on the surface," Crouzier says.
Some synthetic polymers such as polyethylene glycol (PEG) share mucin's ability to hydrate and lubricate surfaces. Crouzier found that grafting polyethylene glycol to mucins stripped of sugars could recover some of their lost lubricative and wetting properties. A sugar-binding lectin (wheat germ agglutinin, or WGA) was used to link the polyethylene glycol to the mucins.
Although Crouzier's demonstration that polyethylene glycol could bind to mucin in place of sugars presents a clear biological-engineering solution to a common problem, much more work will be necessary before it can be implemented in commercial products. Lectins such as WBA can be toxic to certain types of cells. However, in preliminary studies Crouzier conducted with bacteria, immune cells and zebra fish embryos, "we saw that lectins alone at high concentration can be toxic, but once attached to the polyethylene glycol, they lose their toxicity," Crouzier says.
Written by Denis Paiste, Materials Processing Center.
Dissecting the inner workings of mucus barrier could yield better drugs, prevent disease
Call it slime, call it snot, or just call it mucus – this slippery substance serves vital functions in our bodies. Cystic fibrosis, premature child birth and dry eye are all linked to unhealthy changes in the bodily mucus that limits bad germs and lubricates the lungs, eyes and other organs.
Katharina Ribbeck, the Eugene Bell Career Development Professor of Tissue Engineering at MIT, is leading an effort to understand how mucus works and to develop substitutes for when natural mucus production fails.
Katharina Ribbeck, the Eugene Bell Career Development Professor of Tissue Engineering at MIT, diagrams the molecular structure of mucin, which has a protein backbone and a brush-like array of attached sugars, or glycans. Photo: Denise MacPhail
Her research could help engineer new molecular structures that could prevent the passage of harmful germs while promoting drug absorption. It could also lead to a molecular diagnostic test for increased risk of premature birth.
Saliva, tear fluids and internal mucus that have wetting, lubricating and germ-blocking properties. The average person produces about a gallon of mucus each day, and it covers a very large surface area of wet cells in the body. "Your mouth and nose contain very delicate cells that have to be embedded in water all the time," Ribbeck says. When mucus dries out, the cells they protect don't work as well." Healthy mucus is remarkable for its ability to absorb large amounts of water.
Ribbeck is working to change the common perception of mucus, demonstrating that it not merely an "icky" waste product but a fascinating material with many important functions for health. (See related video.)
Mucus depends on mucins, biopolymers with a protein backbone and attached forest of sugar molecules. Tear fluid, for example, contains proteins, salt and mucins. The mucins provide the lubrication that lets the eyelid slide smoothly. Chronic dry eye results from a lack of mucins, and current remedies are less than ideal. "Artificial tear fluids contain the salt, but they lack the mucins, or mucin-like polymers. There are many others – artificial saliva, for example."
Keeping microbes in check
For a long time, Ribbeck says, mucus was thought to function mostly as a structural barrier to germs. But her lab's research has shown that mucus does much more. "The picture is emerging that mucus is very good at preventing virulence of certain microbes," Ribbeck says. "Mucus has the ability to keep microbes in check – to keep them in a commensal, compatible way, so that they live on us but don't cause harm.
"This is different from the way antibiotics work. Antibiotics kill bacteria. Mucus doesn't kill them, but it prevents them from doing bad things, for example, colonizing your epithelial surfaces, wet surfaces, and expressing certain virulence factors," Ribbeck said. Mucus can also keep yeast such as Candida albicans from making the transition to a hyphal form with long filaments that can damage the epithelia. "Yeast cells in mucins remain in the benign form, which the body presumably can tolerate," she says. "We think mucin prevents their virulence."
"We are asking how microbes change their behavior when they get exposed to the mucins," Ribbeck says. "Bit by bit, with genetic perturbations of the microbes, and biochemical dissection of the mucins, we can begin to understand the mechanisms of interaction between the mucins and the microbes."
Mucins have also evolved strategies to prevent viral infections. "We're just beginning to understand how they do that," Ribbeck says. "But it looks like they can act against a broad range of different viruses that are experts in infecting mucosal epithelia. HIV, influenza, papilloma virus, herpes virus – all need to pass through mucus to achieve infection, and usually your mucus is really good at preventing them from passing through. We're dissecting the mechanisms now by which the mucins do that, to then build synthetic molecules that can do the same job."
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Predicting preterm birth risk
Another place mucus operates is in the cervix. During pregnancy, a dense plug of mucus in the cervical canal prevents germs from entering the uterus and harming the developing fetus. Uterine infection is a well-documented cause of premature birth. A diagnostic test to determine risk of premature birth could reduce health-care costs and improve care for mothers and babies. At least one of every 10 babies born worldwide is born prematurely, and premature births add $26 billion to the U.S. health-care price tag every year, according to a 2006 report.
In collaboration with Dr. Michael House, assistant professor of maternal-fetal medicine at Tufts University School of Medicine, Ribbeck's lab is studying cervical mucus with the aim of developing a simple molecular test that could determine risk for preterm birth. In general, the lab is looking for molecular fingerprints for healthy and diseased mucus across the different surfaces of the body. It's still a relatively young field, said Ribbeck, who started the work at Harvard in 2007.
Controlling ionic charge
Leon Li , a post-doctoral associate in Ribbeck's group, demonstrated that ionic charges on molecules and the spatial arrangement of those charges each play a key role in transport through mucus. (See related story.) Li tested positively charged peptides, negatively charged peptides and peptides carrying a mix of negative and positive charges in two different arrangements to show that that spatial arrangements of ionic charge can affect transport.
The new findings point to a new tool for designing drug and gene carriers – specific surface charge configurations to optimize interactions with mucins in mucus for diseases such as cystic fibrosis and gastric ulcers.
Recovering water-absorbing capacity
In collaboration with Johnson and Johnson, MIT post-doctoral associate Thomas Crouzier showed that removing sugars from pig gastric mucin (PGM) weakens its lubricating and water-absorbing capacities. But Crouzier's research showed that substituting a lectin-polyethylene glycol compound for the sugar in partially stripped PGM almost completely restored its water-absorbing capacity, and partially restored its lubricating capacity. The research team's paper is still in process. (See related story.)
"Now we know where to begin," Ribbeck says. "Deciphering the contribution of the mucin-associated glycans, also for lubrication, and then, importantly, developing a simple strategy for recovery, is exciting. This is a first step in the direction of creating synthetic mucins, and we're following up on that in different ways," Ribbeck said.
Written by Denis Paiste, Materials Processing Center.