Category Archives: Transhuman News

2014-10-25 "Design and DNA" - Timothy Standish, PhD
Fourth Presentation in "The Bible, Science And Origin Of Life" series held on Saturday afternoon.

By: Adventisti Toronto

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2014-10-25 "Design and DNA" - Timothy Standish, PhD - Video

The very same building blocks that make us have been successfully programmed to form 32 differently-shaped crystal structures. The structures feature a precisely-defined depth and a variety of sophisticated 3D nanoscale attributes, thereby laying further foundations for the use of DNA to revolutionize nanotechnology.

The news comes courtesy of scientists at Harvard's Wyss Institute for Biologically Inspired Engineering, which previously developed a DNA-brick self-assembly method to create over 100 complex 3D nanostructures about the size of viruses. That prior work made possible the creation of these new DNA crystals, which are more than 1,000 times larger than the older DNA brick structures large enough now that they are comparable to a speck of dust.

"We are very pleased that our DNA brick approach has solved this challenge," said senior author Peng Yin, "and we were actually surprised by how well it works."

The technique is modeled after the way in which Lego bricks interlock to build complex structures. This is possible thanks to the basic rules of DNA mixing: in forming base pairs, the A (adenine) nucleobase only binds to the T (thymine) one while C (cytosine) only binds with G (guanine). Combine many bases, changing the orientation by 90 degrees at each pairing, and you have a DNA brick.

To build their large DNA crystals, the researchers developed cuboid bricks with dimensions six helices by six helices by 24 bases that were selected to bind to the faces of other cuboid bricks. They designed four groups of crystals: one-dimensional Z-crystals and X-crystals that extended along the z axis and x axis, respectively, along with two-dimensional ZX-crystals and XY-crystals.

By combining the bricks in different patterns, they could form large numbers of distinct crystals across these categories, with simple modular design on the computer followed by self-assembly on the part of the DNA strands allowing both great precision and near infinite potential at scales up to 80 nanometers (and perhaps more in the future).

What's more, the technique could enable scalable production of new and emerging technologies, such as quantum computers. The team demonstrated that self-assembled DNA crystals made from these bricks could house gold nanoparticles inserted into slots less than two nanometers apart from each other along the crystal structure a feat that's important for strong plasmonic coupling, which would make the technique useful in photovoltaic devices like solar cells.

The researchers expect DNA crystals to also prove useful in developing more versatile inorganic circuits and other nanoscale technologies. The technique could also aid in protein crystallography, which studies protein structures at atomic resolutions for applications in biotechnology, pharmaceuticals, and the academic field of structural biology.

"DNA nanotechnology now makes it possible for us to assemble, in a programmable way, prescribed structures rivaling the complexity of many molecular machines we see in nature," said co-author William Shih.

A paper describing the DNA brick crystals was published in the journal Nature Chemistry.

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Large 3D nanostructures built from Lego-like DNA bricks

Adherent cells, the kind that form the architecture of all multi-cellular organisms, are mechanically engineered with precise forces that allow them to move around and stick to things. Proteins called integrin receptors act like little hands and feet to pull these cells across a surface or to anchor them in place. When groups of these cells are put into a petri dish with a variety of substrates they can sense the differences in the surfaces and they will "crawl" toward the stiffest one they can find.

Now chemists have devised a method using DNA-based tension probes to zoom in at the molecular level and measure and map these phenomena: How cells mechanically sense their environments, migrate and adhere to things.

Nature Communications published the research, led by the lab of Khalid Salaita, assistant professor of biomolecular chemistry at Emory University. Co-authors include mechanical and biological engineers from Georgia Tech.

Using their new method, the researchers showed how the forces applied by fibroblast cells is actually distributed at the individual molecule level. "We found that each of the integrin receptors on the perimeter of cells is basically 'feeling' the mechanics of its environment," Salaita says. "If the surface they feel is softer, they will unbind from it and if it's more rigid, they will bind. They like to plant their stakes in firm ground."

Each cell has thousands of these integrin receptors that span the cellular membrane. Cell biologists have long been focused on the chemical aspects of how integrin receptors sense the environment and interact with it, while the understanding of the mechanical aspects lagged. Cellular mechanics is a relatively new but growing field, which also involves biophysicists, engineers, chemists and other specialists.

"Lots of good and bad things that happen in the body are mediated by these integrin receptors, everything from wound healing to metastatic cancer, so it's important to get a more complete picture of how these mechanisms work," Salaita says.

The Salaita lab previously developed a fluorescent-sensor technique to visualize and measure mechanical forces on the surface of a cell using flexible polymers that act like tiny springs. These springs are chemically modified at both ends. One end gets a fluorescence-based turn-on sensor that will bind to an integrin receptor on the cell surface. The other end is chemically anchored to a microscope slide and a molecule that quenches fluorescence. As force is applied to the polymer spring, it extends. The distance from the quencher increases and the fluorescent signal turns on and grows brighter. Measuring the amount of fluorescent light emitted determines the amount of force being exerted.

Yun Zhang, a co-author of the Nature Communications paper and a graduate student in the Salaita lab, had the idea of using DNA molecular beacons instead of flexible polymers. "She was new to the lab and brought a fresh perspective," Salaita says.

The molecular beacons are short pieces of lab-synthesized DNA, each consisting of about 20 base pairs, used in clinical diagnostics and research. The beacons are called DNA hairpins because of their shape.

The thermodynamics of DNA, its double-strand helix structure and the energy needed for it to fold are well understood, making the DNA hairpins more refined instruments for measuring force. Another key advantage is the fact that their ends are consistently the same distance apart, Salaita says, unlike the random coils of flexible polymers.

Originally posted here:
Molecular beacons shine light on how cells 'crawl'