Monday, May 28, 2007

Lights, Camera, Action


Romania ete ...!
Vive la Romania !
CANNES, France, May 27 -- The international critics corps can be a tough crowd (if they don't like a film here, they boo), but they mostly agreed that the 60th anniversary of the Cannes Film Festival presented an especially strong slate of movies. At the awards ceremony at the Palais on Sunday evening, the head of the jury, British director Stephen Frears ("The Queen"), praised the selections. "I am told by people who come every year that this was a terrific festival. Thank you. The films were a pleasure to watch." They were also tough to watch, with meditations and stories about evil, sickness and death -- but filled, too, with the triumph, or sometimes just the mere survival, of the human spirit.
And so it was no surprise that the top prize, the Palme d'Or, went to one of the darlings of the festival, "4 Months, 3 Weeks and 2 Days," from Romanian director Cristian Mungiu. The film is set in 1987 Bucharest, during the waning years of the Soviet bloc. It tells the story of a college student who has an illegal abortion, her friend and the abortionist, who is also a rapist. Whew, no?
At the end of a long day in the lab, what we'd all like is an award-winning movie. What makes for a good movie? An engrossing story, deft cinematography, and an extraordinary ensemble of actors. Cannes do not offer something like that so back to nanotechnologies until Eurabians will grow up. The goal of single-molecule research is to produce a movie of the cell. Biochemistry and biophysics done in the test tube already provide an understanding of the dynamic behavior of molecules; from these studies, what goes on in cells, minute by minute or even second by second, can be inferred.
Ultimately, however, the goal is to film single molecules in single cells, focusing in closely enough not only to observe spatial and temporal characteristics but also to decipher molecular mechanisms. We're not there yet, but recent advances in single-molecule techniques bring us tantalizingly close to a molecule-scale movie of cellular life.Because cells are optically transparent, light microscopy is ideal for noninvasive imaging of cells in three dimensions. However, until recently, the resolution of lens-based optical microscopes was constrained by the diffraction barrier, which gave a resolution cutoff at half the wavelength of light. In his Review, Hell (p. 1153) discusses concepts that show how the diffraction barrier can be broken in fluorescence spectroscopy and how these techniques have been applied to achieve nanoscale resolution. His Review gives hope that real-time three-dimensional imaging of live cells with electron-microscopy resolution may not be too far away.
sciencemag
Post Coms
Technorati Cosmos: other blogs commenting on this post

Sunday, May 27, 2007

Origin-Of-Life Researcher Dies

Stanley L. Miller
The chemist known as the father of origin-of-life chemistry, Stanley L. Miller, died on May 20 at age 77. Miller was emeritus professor of chemistry and biochemistry at the University of California, San Diego. He had suffered a series of strokes that began in 1999.

In the 1950s, Miller, working as a graduate student under the late Nobel Laureate Harold C. Urey at the University of Chicago, performed an experiment demonstrating that organic compounds necessary for the origin of life can be generated from simple molecules under the conditions existing on early Earth (Science 1953, 117, 528; J. Am. Chem. Soc. 1955, 77, 2351).

To mimic the ocean/atmosphere system of early Earth, Miller put water and ammonia into a flask with hydrogen and methane gas, boiled the solution, and sparked the contents with an electrical discharge to simulate lightning. Several days later, the solution turned dark brown. Miller analyzed the solution and detected the presence of at least two amino acids. Unconvinced by the results, Miller repeated the experiment and got at least five amino acids—and in large amounts.


Marxist teachers emphasized for me this experiment. Instead to accept their point of view, I have learn that several days means 500 hrs. and the chemist is a sceptical person.

Yes, I have the few building blocks of life. Where it is the cement?

I will burn a candle for Stanley L. Miller


Technorati Cosmos: other blogs commenting on this post

Saturday, May 26, 2007

Nanosensor

Molecular switches
The simplest active DNA nanostructures are switches or actuators that can be driven between two conformations. Motion is induced by changes in temperature or ionic conditions, or by the binding of a signalling molecule, often a DNA strand.
nanosensor
Conformation changes induced by changes in environment
Rotary motion can be produced by changing the twist of DNA. Double-stranded DNA with the sequence (CG)n can be flipped from the usual right-handed helix (B-DNA) to a left-handed conformation (Z-DNA). This transition is favoured by high salt concentrations and low temperatures13. One of the earliest nanomechanical DNA devices14 used this transition to change the angle between two rigid DNA tiles connected by a (CG)10 stem. Each tile carried a reporter fluorophore. Förster resonant energy transfer (FRET) between fluorophores allows sensitive measurement of their separation on a nanometre length scale: the efficiency of energy transfer, mediated by a dipole - dipole interaction, scales as the inverse sixth power of their separation15. When the B - Z transition was induced by an increase in ionic strength, FRET measurements showed an increase in the separation between the fluorophores consistent with the expected relative rotation of the tiles by 3.5 turns.

Yang and co-workers converted changes in the twist of DNA into linear motion16. Their device consisted of a closed loop of double-stranded DNA attached to opposite arms of a four-arm Holliday junction (Box 1)17. A Holliday junction can migrate (isomerize) by breaking identical base pairs in one pair of opposite arms and remaking them in the other pair. A change in the conformation of the DNA within the loop was initiated by adding ethidium bromide: this intercalating dye binds between adjacent base pairs, lengthening and partially unwinding the double helix. The resulting stress was relieved by junction migration: by shortening the protruding arms of the junction the loop was allowed to lengthen without changing the total number of twists within it.

Environmentally driven changes in the conformation of single-stranded DNA can induce linear motion. Under slightly acidic conditions, a single strand with appropriately spaced cytosine bases folds into an i-motif " a compact three-dimensional structure that is held together by cytosine-protonated-cytosine base pairs18. In the presence of a near-complementary strand of DNA there is competition between the i-motif and an extended double helix formed by hybridization of the two strands (note that a perfectly complementary strand would itself fold into a stable structure called the G-quadruplex19). The i-motif device can be switched between compact and extended states by changing the pH20, 21. Cyclic switching can be driven by an oscillating chemical reaction22, 23.

The i-motif-to-duplex transition has been made to do mechanical work. One surface of a silicon cantilever was coated with tethered cytosine-containing strands and formation of the i-motif induced a compressive surface stress that bent the cantilever24. The origin of the surface stress, which is also observed when complementary strands hybridize to tethered probes25, is not understood. Electrostatic repulsion between the compact i-motifs plays a part, but the effect persists with high salt concentrations at which interactions over a distance comparable to the separation between strands are effectively screened.

It has also been suggested that the conformational change resulting from pH-dependent binding of a single strand of DNA to a duplex to form a triple-helical structure could be used as the basis of a nanomechanical actuator26, 27.

Devices such as those described above can be used to monitor and report on their environment. Box 2 describes how active DNA nanostructures are being developed as sensors, how elementary logical operations can be performed on their outputs, and how the combination of sensors and computation might be used to create smart drug-delivery systems.

Conformation changes induced by signalling
Yurke and co-workers28 constructed a pair of DNA tweezers with two rigid double-stranded arms connected at one end by a flexible single-stranded hinge (Fig. 2). In the open configuration, the arms rotate freely about the hinge. Single-stranded tails extend from the free end of both arms and serve as attachment points for a control strand — the 'set' or 'fuel' strand — that can pull the arms together by hybridizing to both of them. A short region of the set strand remains single-stranded even when hybridized to the device: it serves as a toehold for hybridization of a complementary 'unset' or 'antifuel' strand that strips the set strand from the device by branch migration (Box 1). Displacement of the set strand generates a double-stranded waste product and resets the device to its initial open configuration. The device can be driven through many cycles of operation simply by repeated sequential addition of set and unset strands. The time to half completion of a single switching operation is 10 s at typical (micromolar) control-strand concentrations: the rate constant for toehold-mediated strand exchange is 105 M-1 s-1 (ref. 29). Operation of the DNA tweezers has recently been characterized using single molecule FRET measurements30.

Figure 2: A DNA nanomachine driven by repeated sequential addition of DNA control strands.
DNA tweezers28 have two double-stranded arms connected by a flexible single-stranded hinge. The 'set' strand pulls the arms into a closed conformation by hybridizing to single-stranded tails at the ends of the arms. A short region of the set strand remains single-stranded even when it is hybridized to the tweezers: this region serves as a toehold that allows the 'unset' strand to hybridize to the set strand and strip it from the device, returning the tweezers to the open configuration and generating a double-stranded waste product. The state of the device can be determined by measuring the separation between donor and acceptor fluorophores (represented by the green triangle and red circle) using FRET.




Strand displacement has been used to effect conformation changes in a wide variety of systems. A number of variations on the tweezers have been reported including a device where the arms are pushed apart instead of being pulled together31 and a three-state device32. Yan and co-workers33 constructed a linear array of rigid DNA tiles in which adjacent tiles could be flipped between cis and trans conformations by stripping away and replacing control strands. Different conformations were easily distinguished by atomic force microscopy. The same device has recently been incorporated into a two-dimensional DNA array34. Feng et al.35 created a two-dimensional array that could be switched between states with different lattice spacings and Hazarika and co-workers36 used strand displacement to reverse the aggregation of gold nanoparticles held together by DNA bridges37. A number of groups have used DNA control strands to switch a section of DNA between a single-stranded state, designed to fold into a compact G-quadruplex stabilized by hydrogen-bonded tetrads of guanine19, and an extended duplex38, 39, 40.

Motion of DNA devices can be triggered using RNA control strands41. By using a specific messenger RNA (mRNA) as a control strand, a tweezer device has been used to sense in vitro transcription42, 43. These experiments show how DNA devices could be controlled by transcriptional circuits44, 45, 46, 47, and point to future applications in which the presence of a specific mRNA within a cell might trigger an event such as the release of a caged drug48.

The maximum force exerted by hybridization of a signalling strand of DNA can be estimated as the free energy change of hybridization divided by the distance through which the hybridizing strands must move together, and is of the order of 10 pN (ref. 28). The fact that protein motors generate similar forces49, 50, 51, 52 encourages speculation that DNA hybridization could be used to drive DNA devices that mimic natural molecular motors.

Strand displacement has been used to effect conformation changes in a wide variety of systems. A number of variations on the tweezers have been reported including a device where the arms are pushed apart instead of being pulled together31 and a three-state device32. Yan and co-workers33 constructed a linear array of rigid DNA tiles in which adjacent tiles could be flipped between cis and trans conformations by stripping away and replacing control strands. Different conformations were easily distinguished by atomic force microscopy. The same device has recently been incorporated into a two-dimensional DNA array34. Feng et al.35 created a two-dimensional array that could be switched between states with different lattice spacings and Hazarika and co-workers36 used strand displacement to reverse the aggregation of gold nanoparticles held together by DNA bridges37. A number of groups have used DNA control strands to switch a section of DNA between a single-stranded state, designed to fold into a compact G-quadruplex stabilized by hydrogen-bonded tetrads of guanine19, and an extended duplex38, 39, 40.

Motion of DNA devices can be triggered using RNA control strands41. By using a specific messenger RNA (mRNA) as a control strand, a tweezer device has been used to sense in vitro transcription42, 43. These experiments show how DNA devices could be controlled by transcriptional circuits44, 45, 46, 47, and point to future applications in which the presence of a specific mRNA within a cell might trigger an event such as the release of a caged drug48.

The maximum force exerted by hybridization of a signalling strand of DNA can be estimated as the free energy change of hybridization divided by the distance through which the hybridizing strands must move together, and is of the order of 10 pN (ref. 28). The fact that protein motors generate similar forces49, 50, 51, 52 encourages speculation that DNA hybridization could be used to drive DNA devices that mimic natural molecular motors.





Technorati Cosmos: other blogs commenting on this post

Friday, May 11, 2007

DNA nanomachines


Review
----------------------------------------------------------
Nature Nanotechnology 2, 275 - 284 (2007)doi:10.1038/nnano.2007.104
DNA nanomachines
Jonathan Bath1 & Andrew J. Turberfield1
----------------------------------------------------------
Abstract
We are learning to build synthetic molecular machinery from DNA. This research is inspired by biological systems in which individual molecules act, singly and in concert, as specialized machines: our ambition is to create new technologies to perform tasks that are currently beyond our reach. DNA nanomachines are made by self-assembly, using techniques that rely on the sequence-specific interactions that bind complementary oligonucleotides together in a double helix. They can be activated by interactions with specific signalling molecules or by changes in their environment. Devices that change state in response to an external trigger might be used for molecular sensing, intelligent drug delivery or programmable chemical synthesis. Biological molecular motors that carry cargoes within cells have inspired the construction of rudimentary DNA walkers that run along self-assembled tracks. It has even proved possible to create DNA motors that move autonomously, obtaining energy by catalysing the reaction of DNA or RNA fuels.
--------------------------------------------------------------------------------
Introduction
The remarkable specificity of the interactions between complementary nucleotides makes DNA a useful construction material: interactions between short strands of DNA can be controlled with confidence through design of their base sequences (Box 1) The building material. http://www.nature.com/nnano/journal/v2/n5/box/nnano.2007.104_BX1.html
The construction of branched junctions between double helices1 makes it possible to create complex three-dimensional objects2, 3, 4, 5, such as the tetrahedron5 shown in Fig. 1, by self-assembly. One way to exploit this extraordinarily precise architectural control is to use self-assembled DNA templates to position functional molecules: examples include molecular electronic circuits6, 7, near-field optical devices8 and enzyme networks9.
Figure 1: Self-assembly of a nanometre-scale object.The DNA tetrahedron5 has relatively stiff double-stranded edges linked by flexible single-stranded hinges. A cargo, for example a protein48, can be trapped in the central cavity of the tetrahedron. Mechanical devices built from DNA could be used to open the tetrahedron (R. P. Goodman, M. Heilemann, A. N. Kapenidis & A.J.T., manuscript in preparation) to control access to the cargo.
Fig 1



It is an obvious extension of this research to convert static DNA structures into machines. DNA is not the natural choice of material to build active structures with because it lacks the structural and catalytic versatility of proteins and RNA (for both DNA and RNA, Watson–Crick base pairing is the strongest interaction determining inter- and intramolecular interactions, but RNA has a much richer repertoire of weaker non-covalent interactions that can stabilize complex structures10). If we could cope with the interactions required for a three-dimensional fold we would design more competent machines made, as in nature, from RNA and proteins11, 12. We make nanomachines from DNA because the simplicity of its structure and interactions allows us to control its assembly.
In this review we concentrate on research that is leading towards the development of synthetic molecular motors. We start by showing how DNA nanostructures can be made to switch between two states in response to molecular or environmental signals; we describe how a device can be moved along a track by operating molecular switches in the correct sequence; we finish with an account of the current state of development of autonomous molecular motors that are inspired by the natural protein motors myosin and kinesin. Closely related work on DNA sensors and DNA-templated chemistry is described briefly in Boxes 2 (Sensors that can process information






Thursday, May 10, 2007

nsf.gov - News - The Longest Carbon Nanotubes You've Ever Seen - US National Science Foundation (NSF)

nsf.gov - News - The Longest Carbon Nanotubes You've Ever Seen - US National Science Foundation (NSF)

May 10, 2007
Using techniques that could revolutionize manufacturing for certain materials, researchers have grown carbon nanotubes that are the longest in the world. While still slightly less than 2 centimeters long, each nanotube is 900,000 times longer than its diameter.
The fibers--which have the potential to be longer, stronger and better conductors of electricity than copper and many other materials--could ultimately find use in smart fabrics, sensors and a host of other applications.
"This process is revolutionary because it allows us to keep the catalyst 'alive' for a long period of time thus, providing fast and continuous transport of the carbon 'building blocks' to the carbon nanotube growth zone," said Shanov.
More important for manufacturing, the research team grew a 12-millimeters-thick, uniform carpet of aligned carbon nanotubes on a roughly 10-centimeter silicon substrate, opening the door for scaling-up the process.
The inventions were presented in April 2007 at the Single Wall Carbon Nanotube Nucleation and Growth Mechanisms workshop organized by NASA and Rice University.