Tag Archives: Tufts University

Producing stronger silk musically

Markus Buehler and his interdisciplinary team (my previous posts on their work includes Gossamer silk that withstands hurricane force winds and Music, math, and spiderwebs) have synthesized a new material based on spider silk. From the Nov. 28, 2012 news item on ScienceDaily,

Pound for pound, spider silk is one of the strongest materials known: Research by MIT’s [Massachusetts Institute of Technology] Markus Buehler has helped explain that this strength arises from silk’s unusual hierarchical arrangement of protein building blocks.

Now Buehler — together with David Kaplan of Tufts University and Joyce Wong of Boston University — has synthesized new variants on silk’s natural structure, and found a method for making further improvements in the synthetic material.

And an ear for music, it turns out, might be a key to making those structural improvements.

Here’s Buehler describing the work in an MIT video clip,

The Nov. 28, 2012 MIT news release by David Chandler provides more details,

Buehler’s previous research has determined that fibers with a particular structure — highly ordered, layered protein structures alternating with densely packed, tangled clumps of proteins (ABABAB) — help to give silk its exceptional properties. For this initial attempt at synthesizing a new material, the team chose to look instead at patterns in which one of the structures occurred in triplets (AAAB and BBBA).

Making such structures is no simple task. Kaplan, a chemical and biomedical engineer, modified silk-producing genes to produce these new sequences of proteins. Then Wong, a bioengineer and materials scientist, created a microfluidic device that mimicked the spider’s silk-spinning organ, which is called a spinneret.

Even after the detailed computer modeling that went into it, the outcome came as a bit of a surprise, Buehler says. One of the new materials produced very strong protein molecules — but these did not stick together as a thread. The other produced weaker protein molecules that adhered well and formed a good thread. “This taught us that it’s not sufficient to consider the properties of the protein molecules alone,” he says. “Rather, [one must] think about how they can combine to form a well-connected network at a larger scale.”

The different levels of silk’s structure, Buehler says, are analogous to the hierarchical elements that make up a musical composition — including pitch, range, dynamics and tempo. The team enlisted the help of composer John McDonald, a professor of music at Tufts, and MIT postdoc David Spivak, a mathematician who specializes in a field called category theory. Together, using analytical tools derived from category theory to describe the protein structures, the team figured out how to translate the details of the artificial silk’s structure into musical compositions.

The differences were quite distinct: The strong but useless protein molecules translated into music that was aggressive and harsh, Buehler says, while the ones that formed usable fibers sound much softer and more fluid.

Combining materials modeling with mathematical and musical tools, Buehler says, could provide a much faster way of designing new biosynthesized materials, replacing the trial-and-error approach that prevails today. Genetically engineering organisms to produce materials is a long, painstaking process, he says, but this work “has taught us a new approach, a fundamental lesson” in combining experiment, theory and simulation to speed up the discovery process.

Materials produced this way — which can be done under environmentally benign, room-temperature conditions — could lead to new building blocks for tissue engineering or other uses, Buehler says: scaffolds for replacement organs, skin, blood vessels, or even new materials for use in civil engineering.

It may be that the complex structures of music can reveal the underlying complex structures of biomaterials found in nature, Buehler says. “There might be an underlying structural expression in music that tells us more about the proteins that make up our bodies. After all, our organs — including the brain — are made from these building blocks, and humans’ expression of music may inadvertently include more information that we are aware of.”

“Nobody has tapped into this,” he says, adding that with the breadth of his multidisciplinary team, “We could do this — making better bio-inspired materials by using music, and using music to better understand biology.”

At the end of Chandler’s news release there’s a notice about a summer course with Markus Buehler,

For those interested in the work Professor Buehler is doing, you may also be interested to know that he is offering a short course on campus this summer called Materials By Design.

Materials By Design
June 17-20, 2013
shortprograms.mit.edu/mbd

Through lectures and hands-on labs, participants will learn how materials failure, studied from a first principles perspective, can be applied in an effective “learning-from-failure approach” to design and make novel materials. Participants will also learn how superior material properties in nature and biology can be mimicked in bioinspired materials for applications in new technology. This course will be of interest to scientists, engineers, managers, and policy makers working in the area of materials design, development, manufacturing, and testing. [emphasis mine]

I wasn’t expecting to see managers and policy makers as possible students for this course.

By the way, Buehler is not the only scientist to make a connection between music and biology (although he seems to be the only person using the concept for applications), there’s also geneticist and biophysicist, Mae Wan Ho and her notion of quantum jazz. From the Quantum Jazz Biology* article by David Reilly in the June 23, 2010 Isis Report,

I use the analogy of ‘quantum jazz’ to express the quantum coherence of the organism. It goes through a fantastic range of space and time scales, from the tiniest atom or subatomic particle to the whole organism and beyond. Organisms communicate with other organisms, and are attuned to natural rhythms, so they have circadian rhythms, annual rhythms, and so on. At the other extreme, you have very fast reactions that take place in femtoseconds. And all these rhythms are coordinated, there is evidence for that.

Tooth tattoos at Tufts University

In spring 2012, there was a fluttering in the blogosphere about tooth tattoos with the potential for monitoring dental health. As sometimes happens, I put off posting about the work until it seemed everyone else had written about it (e.g. Mar. 30, 2012 posting by Dexter Johnson for his Nanoclast blog on the IEEE website) and there was nothing left for me to say.  Happily, the researchers at Tufts University (where part of this research [Princeton University is also involved] is being pursued) have released more information in a Nov. 1, 2012 news article by David Levin,

The sensor, dubbed a “tooth tattoo,” was developed by the Princeton nanoscientist Michael McAlpine and Tufts bioengineers Fiorenzo Omenetto, David Kaplan and Hu Tao. The team first published their research last spring in the journal Nature Communications.

The sensor is relatively simple in its construction, says McAlpine. It’s made up of just three layers: a sheet of thin gold foil electrodes, an atom-thick layer of graphite known as graphene and a layer of specially engineered peptides, chemical structures that “sense” bacteria by binding to parts of their cell membranes.

“We created a new type of peptide that can serve as an intermediary between bacteria and the sensor,” says McAlpine. “At one end is a molecule that can bond with the graphene, and at the other is a molecule that bonds with bacteria,” allowing the sensor to register the presence of bacteria, he says.

Because the layers of the device are so thin and fragile, they need to be mounted atop a tough but flexible backing in order to transfer them to a tooth. The ideal foundation, McAlpine says, turns out to be silk—a substance with which Kaplan and Omenetto have been working for years.

By manipulating the proteins that make up a single strand of silk, it’s possible to create silk structures in just about any shape, says Omenetto, a professor of biomedical engineering at Tufts. Since 2005, he’s created dozens of different structures out of silk, from optical lenses to orthopedic implants. Silk is “kind of like plastic, in that we can make [it] do almost anything,” he says. “We have a lot of control over the material. It can be rigid. It can be flexible. We can make it dissolve in water, stay solid, become a gel—whatever we need.”

Omenetto, Kaplan and Tao created a thin, water-soluble silk backing for McAlpine’s bacterial sensor—a film that’s strong enough to hold the sensor components in place, but soft and pliable enough to wrap easily around the irregular contours of a tooth.

To apply the sensor, McAlpine says, you need only to wet the surface of the entire assembly—silk, sensor and all—and then press it onto the tooth. Once there, the silk backing will dissolve within 15 or 20 minutes, leaving behind the sensor, a rectangle of interwoven gold and black electrodes about half the size of a postage stamp and about as thick as a sheet of paper. The advantage of being attached directly to a tooth means that the sensor is in direct contact with bacteria in the mouth—an ideal way to monitor oral health.

Because the sensor doesn’t carry any onboard batteries, it must be both read and powered simultaneously through a built-in antenna. Using a custom-made handheld device about the size of a TV remote, McAlpine’s team can “ping” that antenna with radio waves, causing it to resonate electronically and send back information that the device then uses to determine if bacteria are present.

The sensor (A), attached to a tooth (B) and activated by radio signals (C), binds with certain bacteria (D). Illustration: Manu Mannoor/Nature Communications (downloaded from http://now.tufts.edu/articles/tooth-tattoo)

In addition to its potential for  monitoring dental health, the tooth tattoo could replace some of the more invasive health monitoring techniques (e.g., drawing blood), from the Tufts University article,

In addition to monitoring oral health, Kugel [Gerard Kugel, Tufts professor of prosthodontics and operative dentistry and associate dean for research at Tufts School of Dental Medicine] believes the tooth tattoo might be useful for monitoring a patient’s overall health. Biological markers for many diseases—from stomach ulcers to AIDS—appear in human saliva, he says. So if a sensor could be modified to react to those markers, it potentially could help dentists identify problems early on and refer patients to a physician before a condition becomes serious.

“The mouth is a window to the rest of the body,” Kugel says. “You can spot a lot of potential health problems through saliva, and it’s a much less invasive way to do diagnostic tests than drawing blood.”

Before monitoring of any type can take place, there is at least one major hurdle still be overcome. Humans are quite sensitive to objects being placed in their mouths. According to one of the researchers, we can sense objects that are 50 to 60 microns wide, about the thickness piece of paper, and that may be too uncomfortable to bear.

H/T Nov. 9, 2012 news item on Nanowerk for pointing me towards the latest information about these tooth tattoos.

Organ chips for DARPA (Defense Advanced Research Projects Agency)

The Wyss Institute will receive up to  $37M US for a project that integrates ten different organ-on-a-chip projects into one system. From the July 24, 2012 news release on EurekAlert,

With this new DARPA funding, Institute researchers and a multidisciplinary team of collaborators seek to build 10 different human organs-on-chips, to link them together to more closely mimic whole body physiology, and to engineer an automated instrument that will control fluid flow and cell viability while permitting real-time analysis of complex biochemical functions. As an accurate alternative to traditional animal testing models that often fail to predict human responses, this instrumented “human-on-a-chip” will be used to rapidly assess responses to new drug candidates, providing critical information on their safety and efficacy.

This unique platform could help ensure that safe and effective therapeutics are identified sooner, and ineffective or toxic ones are rejected early in the development process. As a result, the quality and quantity of new drugs moving successfully through the pipeline and into the clinic may be increased, regulatory decision-making could be better informed, and patient outcomes could be improved.

Jesse Goodman, FDA Chief Scientist and Deputy Commissioner for Science and Public Health, commented that the automated human-on-chip instrument being developed “has the potential to be a better model for determining human adverse responses. FDA looks forward to working with the Wyss Institute in its development of this model that may ultimately be used in therapeutic development.”

Wyss Founding Director, Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member, Kevin Kit Parker, Ph.D., will co-lead this five-year project.

I note that Kevin Kit Parker was mentioned in an earlier posting today (July 26, 2012) titled, Medusa, jellyfish, and tissue engineering, and Donald Ingber in my Dec.1e, 2011 posting about Shrilk and insect skeletons.

As for the Wyss Institute, here’s a description from the news release,

The Wyss Institute for Biologically Inspired Engineering at Harvard University (http://wyss.harvard.edu) uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Boston Children’s Hospital, Brigham and Women’s Hospital, , Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Tufts University, and Boston University, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

I hadn’t thought of an organ-on-a-chip as particularly bioinspired so I’ll have to think about that one for a while.

Microneedles from Tufts University

Here’s some very exciting news from Tufts University in a Dec. 21, 2011 news item on Nanowerk,

Bioengineers at Tufts University School of Engineering have developed a new silk-based microneedle system able to deliver precise amounts of drugs over time and without need for refrigeration. The tiny needles can be fabricated under normal temperature and pressure and from water, so they can be loaded with sensitive biochemical compounds and maintain their activity prior to use. They are also biodegradable and biocompatible.

I have previously written about a micro needle project at the Georgia Institute of Technology in Nov. 9, 2011 posting and about Mark Kendall’s nano vaccine patch on more than one occasion, most recently in my Aug. 3, 2011 posting.

This new drug delivery project surprised me; I didn’t realize that horesradish could also be a drug,

The Tufts researchers successfully demonstrated the ability of the silk microneedles to deliver a large-molecule, enzymatic model drug, horseradish peroxidase (HRP), at controlled rates while maintaining bioactivity. In addition, silk microneedles loaded with tetracycline were found to inhibit the growth of Staphylococcus aureus, demonstrating the potential of the microneedles to prevent local infections while also delivering therapeutics.

“By adjusting the post-processing conditions of the silk protein and varying the drying time of the silk protein, we were able to precisely control the drug release rates in laboratory experiments,” said Fiorenzo Omenetto, Ph.D., senior author on the paper. “The new system addresses long-standing drug delivery challenges, and we believe that the technology could also be applied to other biological storage applications.”

If we’re all lucky, it won’t be too long before syringes are a museum item and we’ll be getting our medication with far less discomfort/pain and, in some cases, fear.