Tag Archives: Nadrian Seeman

Nature celebrates some nanotechnology anniversaries

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An April 5, 2016 editorial in Nature magazine celebrates some nanotechnology milestones (Note: Links have been removed),

In March 1986, the atomic force microscope (AFM) was introduced by Gerd Binnig, Calvin Quate and Christoph Gerber with a paper in the journal Physical Review Letters titled simply ‘Atomic force microscope’1. This was 5 years (to the month) after the precursor to the AFM, the scanning tunnelling microscope (STM), had first been successfully tested at IBM’s Zurich Research Laboratory by Binnig and the late Heinrich Rohrer, and 7 months before Binnig and Rohrer were awarded a share of the Nobel Prize in Physics for the design of the STM (the prize was shared with Ernst Ruska, the inventor of the electron microscope). Achieving atomic resolution with the AFM proved more difficult than with the STM. It was, for example, only two years after its invention that the STM provided atomic-resolution images of an icon of surface science, the 7 × 7 surface reconstruction of Si(111) (ref. 2), whereas it took 8 years to achieve a similar feat with the AFM3, 4.

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The editorial also provides an explanation of how the AFM works,

The AFM works by scanning a sharp tip attached to a flexible cantilever across a sample while measuring the interaction between the tip and the sample surface. The technique can operate in a range of environments, including in liquid and in air, and unlike the STM, it can be used with insulating materials; in their original paper, Binnig and colleagues used the instrument to analyse an aluminium oxide sample.

Then, the editorial touches on DNA (deoxyribonucleic acid) nanotechnology (Note: Links have been removed),

The history of structural DNA nanotechnology can, like the AFM, be traced back to the early 1980s, when Nadrian Seeman suggested that the exquisite base-pairing rules of DNA could be exploited to build artificial self-assembled structures11. But the founding experiment of the field came later. In April 1991, Seeman and Junghuei Chen reported building a cube-like molecular complex from DNA using a combination of branched junctions and single-stranded ‘sticky’ ends12. A range of significant advances soon followed, from 2D DNA arrays to DNA-based nanomechanical devices.

Then, in March 2006, the field of structural DNA nanotechnology experienced another decisive moment: Paul Rothemund reported the development of DNA origami13. This technique involves folding a long single strand of DNA into a predetermined shape with the help of short ‘staple’ strands. Used at first to create 2D structures, which were incidentally characterized using the AFM, the approach was quickly expanded to the building of intricate 3D structures and the organization of other species such as nanoparticles and proteins. …

Happy reading!

Minimalist DNA nanodevices perform bio-analytical chemistry inside live cells

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A comparison of minimalist versus baroque architecture is one of the more startling elements in this March 24, 2016 news item on Nanowerk about a scientist working with DNA (deoxyribonucleic acid) nanodevices,

Some biochemistry laboratories fashion proteins into complex shapes, constructing the DNA nanotechnological equivalent of Baroque or Rococo architecture. Yamuna Krishnan, however, prefers structurally minimalist devices.

“Our lab’s philosophy is one of minimalist design,” said Krishnan, a professor of chemistry at the University of Chicago. “It borders on brutalist. Functional with zero bells and whistles. There are several labs that design DNA into wonderful shapes, but inside a living system, you need as little DNA as possible to get the job done.”

That job is to act as drug-delivery capsules or as biomedical diagnostic tools.

A March 24, 2016 University of Chicago news release by Steve Koppes, which originated the news item, provides some background information before launching into the latest news,

In 2011, Krishnan and her group, then at the National Centre for Biological Sciences in Bangalore, India, became the first to demonstrate the functioning of a DNA nanomachine inside a living organism. This nanomachine, called I-switch, measured subcellular pH with a high degree of accuracy. Since 2011, Krishnan and her team have developed a palette of pH sensors, each keyed to the pH of the target organelle.

Last summer, the team reported another achievement: the development of a DNA nanosensor that can measure the physiological concentration of chloride with a high degree of accuracy.

“Yamuna Krishnan is one of the leading practitioners of biologically oriented DNA nanotechnology,” said Nadrian Seeman, the father of the field and the Margaret and Herman Sokol Professor of Chemistry at New York University. “These types of intracellular sensors are unique to my knowledge, and represent a major advance for the field of DNA nanotechnology.”

Chloride sensor

Chloride is the single most abundant, soluble, negatively charged molecule in the body. And yet until the Krishnan group introduced its chloride sensor—called Clensor—there was no effective and practical way to measure intracellular stores of chloride.

“What is especially interesting about this sensor is that it is completely pH independent,” Seeman said, a significant departure from Krishnan’s previous scheme. “She spent a number of years developing pH sensors that work intra-cellularly and provide a fluorescent signal as a consequence of a shift in pH.”

The ability to record chloride concentrations is important for many reasons. Chloride plays an important role in neurobiology, for example. But calcium and sodium—both positively charged ions—tend to grab most of the neurobiological glory because of their role in neuron excitation.

“But if you want your neuron to fire again, you have to bring it back to its normal state. You have to stop it firing,” Krishnan said. This is called “neuronal inhibition,” which chloride does.

“It’s important in order to reset your neuron for a second round of firing, otherwise we would all be able to use our brains only once,” she said.

Under normal circumstances, the transport of chloride ions helps the body produce thin, freely flowing mucus. But a genetic defect results in a life-threatening disease: cystic fibrosis. Clensor’s capacity to measure and visualize protein activity of molecules like the one related to cystic fibrosis transmembrane could lead to high-throughput assays to screen for chemicals that would restore normal functioning of the chloride channel.

Nine diseases

“One could use this to look at chloride ion channel activity in a variety of diseases,” Krishnan said. “Humans have nine chloride ion channels, and the mutation of each of these channels results in nine different diseases.” Among them are osteopetrosis, deafness, muscular dystrophy and Best’s macular dystrophy.

The pH-sensing capabilities of the I-switch, meanwhile, are important because cells contain multiple organelles that maintain specific values of acidity. Cells need these different microenvironments to carry out specialized chemical reactions.

“Each subcellular organelle has a specific resting value of acidity, and that acidity is crucial to its function,” Krishnan said. “When the pH is not the value that it’s meant to be, it results in a range of different diseases.”

There are 70 rare diseases called lysosomal storage disorders, which are progressive and often fatal. Each one—including Batten disease, Niemann-Pick disease, Pompe disease and Tay-Sachs disease—represents a different way a lysosome can go bad. She likened a defective lysosome to a garbage bin that never gets emptied.

“The lysosome is basically responsible for chewing up all the garbage and making sure it’s either reused or got rid of. It’s the most acidic organelle in the cell.” And that acidity is crucial for the degradation process.

Although there are 70 lysosomal storage diseases, small molecule drugs are available for only a few of them. These existing treatments—enzyme-replacement therapies—are expensive and are only palliative treatments. One goal of Krishnan’s group is to demonstrate the utility of their pH sensors to discover new biological insights into these diseases. Developing small molecule drugs—which are structurally simpler and easier to manufacture than traditional biological drugs—could help significantly.

“If we can do this for one or two lysosomal diseases, there’ll be hope for the other 68,” Krishnan said.

Here are links to and citations for the 2015 and 2011 papers,

A pH-independent DNA nanodevice for quantifying chloride transport in organelles of living cells by Sonali Saha, Ved Prakash, Saheli Halder, Kasturi Chakraborty, & Yamuna Krishnan. Nature Nanotechnology 10, 645–651 (2015)  doi:10.1038/nnano.2015.130 Published online 22 June 2015

An autonomous DNA nanomachine maps spatiotemporal pH changes in a multicellular living organism by Sunaina Surana, Jaffar M. Bhat, Sandhya P. Koushika, & Yamuna Krishnan. Nature Communications 2, Article number: 340  doi:10.1038/ncomms1340 Published 07 June 2011

The 2015 paper is behind a paywall but the 2011 paper is open access.

New York University/Caltech grant is part of the NSF’s Origami Design for Integration of Self-assembling Systems for Engineering Innovation (ODISSEI) program

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The US National Science Foundation (NSF) has an origami program,  Origami Design for Integration of Self-assembling Systems for Engineering Innovation (ODISSEI), which recently announced a $2M grant to New York University (NYU) and the California Institute of Technology (Caltech) to create new nanomaterials according to an Aug. 6, 2013 news item on Nanowerk,

The National Science Foundation (NSF) has awarded New York University researchers and their colleagues at the California Institute of Technology (Caltech) a $2 million grant to develop cutting-edge nanomaterials that hold promise for improving the manufacturing of advanced materials, biofuels, and other industrial products.

Under the grant, the scientists will develop biomimetic materials with revolutionary properties—these molecules will self-replicate, evolve, and adopt three-dimensional structures a billionth of a meter in size by combining DNA-guided self-assembly with the centuries-old art of origami folding.

The Aug. 5, 2013 NYU press release, which originated the news item,  provides details about the researchers and the project,

The four-year grant is part of the NSF’s Origami Design for Integration of Self-assembling Systems for Engineering Innovation (ODISSEI) program and includes NYU Chemistry Professors Nadrian Seeman and James Canary and NYU Physics Professor Paul Chaikin. They will team up with Caltech’s William A. Goddard, III and Si-ping Han.

Others involved in the project are molecular biologists John Rossi and Lisa Scherer of City of Hope Medical Center and mathematicians Joanna Ellis-Monaghan and Greta Pangborn of Saint Michael’s College in Vermont.

The work will build upon recent breakthroughs in the field of structural DNA nanotechnology, which Seeman founded more than three decades ago and is now pursued by laboratories across the globe. His creations allow him to arrange pieces and form specific molecules with precision—similar to the way a robotic automobile factory can be told what kind of car to make.

Previously, Seeman has created three-dimensional DNA structures, a scientific advance bridging the molecular world to the world where we live. To do this, he and his colleagues created DNA crystals by making synthetic sequences of DNA that have the ability to self-assemble into a series of 3D triangle-like motifs. The creation of the crystals was dependent on putting “sticky ends”—small cohesive sequences on each end of the motif—that attach to other molecules and place them in a set order and orientation. The make-up of these sticky ends allows the motifs to attach to each other in a programmed fashion.

Recently, the Seeman and Chaikin labs teamed up to develop artificial structures that can self-replicate, a process that has the potential to yield new types of materials. In the natural world, self-replication is ubiquitous in all living entities, but artificial self-replication had previously been elusive. Their work marked the first steps toward a general process for self-replication of a wide variety of arbitrarily designed “seeds”. The seeds are made from DNA tile motifs that serve as letters arranged to spell out a particular word. The replication process preserves the letter sequence and the shape of the seed and hence the information required to produce further generations. Self-replication enables the evolution of molecules to optimize particular properties via selection processes.

Under the NSF grant, the researchers will aim to take these innovations to the next level: the creation of self-replicating 3D arrays. To do so, the collaborators will aim to fold replicating 1D and 2D arrays into 3D shapes in a manner similar to paper origami—a complex and delicate process.

In meeting this challenge, they will adopt tools from graph theory and origami mathematics to develop algorithms to direct self-assembling DNA nanostructures and their origami folds. The mathematical component of the endeavor will be supplemented by the artistic expertise of Portland, Ore.-based sculptor Julian Voss-Andreae, who will advise the team on issues related to design and will use his skills to develop life-size physical models of the nanoscopic structures the scientists are seeking to build. [emphasis mine]

I wasn’t expecting to see a sculptor included in the team and I wonder if there might be plans to use his sculptures not only as models but also in exhibitions and art shows to fulfill any science outreach requirements that the NSF might have for its grantees.

I did a little further digging into the NSF’s ‘origami’ program and found this webpage explaining that ‘origami’ is part of a still larger program,

The Emerging Frontiers in Research and Innovation (EFRI) office awarded 15 grants in FY 2012, including the following 8 on the topic of Origami Design for Integration of Self-assembling Systems for Engineering Innovation (ODISSEI): …

As there wasn’t any information about grants for FY 2013, I gather they haven’t had time to update the page or add any recent news releases to the website.