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Molecular Motors amazingly designed

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1 Molecular Motors amazingly designed on Wed Jan 22, 2014 1:52 pm


Molecular Motors

The argument from molecular motors and their use in nanotechnology
1. The cell is best described as a miniature factory where literally thousands of machines perform various specialized tasks.
2. These functions include:
a. allowing the cell to replicate itself in less than an hour,
b. proofreading and repairing errors in its own manufacturing instructions (DNA),
c. sensing its environment and responding to it,
d. changing its shape and morphology, and
e. obtaining energy from photosynthesis or metabolism.
3. The devices engineered by man are similar to these molecular motors.
4. These include:
a. “electric” motors having stators, rotors, shafts, bearings and universal joints;
b. transport “trucks” that provide stepwise motion along “highways” called microtubules or filaments;
c. pumps made from tubes and cams1 that force fluids along the tubes.
5. The major differences between these molecular motors and those made by humans are their size (a billion times smaller) and their efficiency (near 100 percent vs. 65 percent, at best).
6. In the last few decades, research efforts in nanotechnology resulted in making various components of machines, like cogwheels2 or pumps, but have not yet been able to produce the motors needed to make the machinery go.
7. Machines found in cells are absolutely extraordinary in their characteristics, inspiring the creativity of the most advanced researchers. However, the cell machines although almost identical in form but different in size are superior in efficiency to the mechanical devices that the best engineers design for everyday life.
8. This indicates that the biomachines found in cells require a level of intelligent design far greater than what man has accomplished.
9. God necessarily exists.

Nature uses tiny nano-machines that could work miracles if we learn how to build them
By Karl Leif Bates


The Nobel Prize-winning physicist Richard Feynman of the California Institute of Technology closed his visionary 1959 talk on the potential of nanotechnology, "There's Plenty of Room at the Bottom," by offering a prize to the first person "who makes a motor which can be controlled from the outside and, not counting the lead-in wires, is only a 1/64 th-inch cube." That's half the thickness of a credit card.

What Feynman didn't realize at the time, and couldn't have known, was that he was already in possession of trillions of devices far smaller and more powerful than he imagined. To utter this challenge and to gesticulate as he spoke, Professor Feynman was relying on the molecular motors and machines that worked within almost every cell throughout his body. Some of them are 20,000 times smaller than the device he imagined and far more efficient than anything our species has ever built.
Kinesin is the miniscule longshoreman of the cell, toting parcels of cargo on its shoulders as it steps along a scaffolding called a microtubule. Each molecule of ATP fuel that kinesin encounters triggers precisely one 8 nanometer step of the longshoreman.

Biology has been using these little machines and motors to operate living cells for millions of years: in bacteria that swim by spinning their hairlike propeller; in the little levers that pull our muscle fibers tight; and in even smaller rotary motors on the surface of mammalian cells that turn in response to a single proton of electrical current.

So, before Feynman even thought of it, nature had nanotechnology nailed.

Rather than starting from scratch to invent Feynman's nano-motor, scientists and engineers at the University of Michigan are looking at these self-assembled, ultra-efficient, incredibly small, natural motors that exist all around us and within us. The blueprints and operating instructions for them are contained within DNA.

"These things are machines!" says Michael Mayer, an assistant professor of chemical and biomedical engineering. "It would be amazing to figure out how to make them."

Like a tiny longshoreman

His colleague, Edgar Meyhöfer, an associate professor of mechanical and biomedical engineering, is particularly interested in a 50-nanometer long machine called a kinesin (ky-nee-sin). This molecule is like a longshoreman walking across the inter-cellular space carrying cargo on its shoulders. One end of the dumbbell-shaped molecule is anchored to a vesicle, a little cargo container within the cell. The other end walks along a length of tube-like material called a microtubule.
Biomedical engineers Hunt (left) and Meyhöfer use an elaborate microscope that relies on `optical tweezers' to feel the tiny forces exerted by molecular motors.

The kinesin molecule will make precisely one 8-nanonometer step in response to one molecule of ATP (adenosine triphosphate), the universal fuel of cells. Click-click-click, it moves along the microtubule in step-wise fashion carrying its cargo, as long as it keeps getting ATP. "Every plant and animal has kinesins." Meyhöfer says. "They are ubiquitous."

Human pathogens have been found to hitch rides around the interior of the host cell on kinesin molecules. The vaccinia virus that causes relatively harmless cowpox and gives us the word vaccine makes its way across the cell in under a minute riding atop a kinesin�a trip that would take more than 10 hours by simple diffusion.

Other infectious agents are suspected of performing the same trick. Interruption of this process might become a new target for anti-bacterial and anti-viral therapies.

Not only is it tiny, kinesin's motor is about 50 percent efficient, which is about twice as good as a gasoline engine. And pound for pound, kinesin produces nearly 15 times more power than that man-made engine.

Meyhöfer and Alan Hunt, an assistant professor of biomedical engineering and gerontology, are experimenting with anchoring kinesins on a firm platform like a sheet of glass and allowing them to shuttle microtubules around overhead. Attach something bigger to the microtubules and you've got a nano-motor or a nano-conveyer belt for a microchip machine.
Molecular motors are on the sub-cellular, nanometer scale.

Hunt shows a black and white movie on his computer monitor. White worm-like shapes are careening around a black space, pretty much at random. Hunt explains that these are pieces of microtubule being shuttled around by a forest of excited kinesins mounted to a piece of glass.

"We would like to be able to put a single molecule into a location and know that it is working," says Meyhöfer. "That is truly nanotechnology."

This collaborative project spans disciplines, and so it also involves collaboration with assistant professors Joe Bull of Department of Biomedical Engineering, Ernest Hasselbrink and Katsuo Kurabayashi of Mechanical Engineering, and Lingjie "Jay" Guo of Electrical Engineering.
Halil Mutlu of Turkey coordinated the activity of billions of myosin motors in his muscles to lift three times his own body weight in the 2004 Olympics.

"One of the limiting factors in MEMS (microchip machines) is a lack of good motors," Hunt says. But these remarkable little machines may do the trick. Hunt's lab has been able to bind kinesin motors to a hard surface in very tight, uniform patterns, and they function perfectly.

Meyhöfer says it also is possible to make a working kinesin even smaller. If you clip out the middle part, it will still work. "I think you could easily fit the whole machine into a 10 nanometer cube." (If this motor were one-inch long, Feynman's motor would be more than half a mile.)

When nanotech is able to make the gears, drive shafts and levers needed by the MEMS devices, they won't be purely mechanical and they won't be hard like silicon. The nanotech parts of these machines will be floppy, more like balloon animals than precision-milled steel. And their actions will be temperature sensitive, more like chemistry.

"At the nano-scale, you cannot separate physics from chemistry from biology, because they are all entwined," Hunt says.

Myosin motors exert a strong tug on the actin filament (red) in muscle cells, causing mechanical contraction of the muscle.

The smallest muscle

The molecular motor that moves our muscles is called myosin , and it looks sort of like a two-legged bug. A molecule of ATP fuel produces one "stroke" of the myosin leg, like a single stroke of a rowing machine. Each stroke produces 3 to 10 piconewtons of power.

"A piconewton is about the gravitational attraction between me and this pen," Hunt says, holding up a dry-erase marker. "Or it's about the pressure exerted by shining a flashlight on a penny."

In fact, the gentle force exerted by light is what Hunt and Meyhöfer use to measure the miniscule power of a single molecular motor. They have one end of a molecule hold on to a tiny plastic bead that is fixed in a cone of tightly focused laser light. Then they pull the bead away "like a spring attached to the wall" and watch how the molecule pulls back against the drag created by the light. The pull of kinesin, for example, is just 4 to 6 piconewtons.

Individually, these motors may not seem like much, acknowledges Meyhöfer, whose doctorate is in zoology. But put millions of myosin motors together in series and in parallel and you have the muscle power that enables 4-foot-11-inch, 123-pound Olympian Halil Mutlu of Turkey to lift 350 pounds over his head.

Topoisomerase is a Pac-Man shaped enzyme that helps DNA molecules untwist. It clips one strand of the double helix, allowing it to relax, and then repairs the clipped spot.

The cell's dynamo

Though it's not a primary focus of his work, Michael Mayer, who trained in chemistry and biophysics, is also intrigued by a 20-nanometer motor called ATP synthase. It's a little rotary motor in the membrane of mitochondria (the cell's power house) that turns in response to incoming protons. Rotation of the motor converts adenosine diphosphate (ADP) molecules into ATP molecules, the cell's fuel.

The ATP-making motor is more than 75 percent efficient, and its design is ancient, appearing in just about every form of life, except for archaea, the forerunners of modern bacteria. It is also constructed to run backwards, a trick some bacteria use to spit out protons in response to ATP.

DNA un-twister

Chemist Ioan Andricioaei takes his telephone off the hook. "This cord is like a DNA helix," he says, spinning the handset to twist the cord until it's a snarled mess. "You have twists on top of twists now, which also happens in DNA."
The ATP Synthase motor has the classic stator and rotor structure familiar in man-made motors. It spans a cellular membrane which admits protons (H+) one at a time. For each proton, the motor turns once, adding a phosphate to adenosine di-phosphate and converting it to adenosine tri-phosphate, the universal fuel source of cells.

But in order for the cellular machinery to read the DNA's crucial genetic information, it has to be more relaxed, so that the spiral molecule can open up. "What would be your strategy for undoing this?"

If it's a phone cord, you can unclip one end and let it relax.

"Exactly!" Andricioaei says. "Nature does the same thing."

The tiny motor that accomplishes the untangling is an enzyme called topoisomerase (toe-po-EYE-so-mare-ays), and its shape resembles a tiny PacMan. The topoisomerase molecule binds to the side of the twisted helix, clips an opening in one of the two spiraling backbones of the DNA, and then lets the thing unwind itself. Once the DNA has relaxed, the enzyme repairs the clipped backbone and goes on its way to find another snarl to work on.

Andricioaei's team is building computer models of a small area of the genome, about 100 angstroms (0.1 nanometer), in which the topoisomerase is at work to see it in motion. Understanding topoisomerase better could lead to cancer drugs that prevent the cancer cell from duplicating itself, Andricioaei says.

The little engine that could

The most efficient, powerful nanomotor found in nature so far is a proton-fueled rotary motor that bacteria use to swim. This motor spins the base of each hair-like flagellum on the bacterium, making the hair into a long propeller.

A single flagellar motor puts out about 20 piconewtons of torque, speeding the bug forward at about 1 micron per second. Its power is stunning: 13,600 watts per kilogram, about 45 times the output of a gasoline engine.

This exquisite little engine could put a great spin on the nanotechnology devices of the future. Learning how to build and operate these machines would lead to the ultimate interface of man and machine.

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2 Re: Molecular Motors amazingly designed on Wed Jan 22, 2014 1:53 pm



Many bacteria, such as Salmonella, Escherichia coli, and some Streptococci, propel themselves with miniature motors at up to 15 body-lengths per second,f equivalent to a car traveling 150 miles per hour—in a liquid. These extremely efficient, reversible motors rotate at up to 100,000 revolutions per minute.g Each shaft rotates a bundle of whiplike flagella that acts as a propeller. The motors, having rotors and stators, are similar in many respects to electrical motors.h However, their electrical charges come from a flow of protons, not electrons. The bacteria can stop, start, and change speed, direction, and even the “propeller’s” shape.i They also have intricate sensors, switches, control mechanisms, and a short-term memory. All this is highly miniaturized. Eight million of these bacterial motors would fit inside the circular cross section of a human hair.

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3 Re: Molecular Motors amazingly designed on Sun Aug 02, 2015 5:29 am


Molecular Machines on the Move 1

Discoveries about the cell's machinery continue to mount. Here's a quick rundown of new findings from the scientific literature about molecular machines, with links for those who want the details.

Librarians: Before the genetic code can be read, genes must be made accessible. Sometimes to get to a gene, the library needs to be remodeled. A paper in PNAS discusses "chromatin remodeling complexes, or remodelers, which are typically large, multisubunit complexes that use an ATPase subunit to translocate the DNA." (Emphasis added.)
Electricians: Another paper in PNAS (open access) begins, "Voltage-gated ion channels support electrochemical activity in cells and are largely responsible for information flow throughout the nervous systems." The paper digs deeper into the voltage sensing of the channels.
Men at work: In some species, males must deliver centrioles to the zygote. A paper in PNAS states, "Our data suggest that the same specialized meiotic mechanisms that function to prevent premature release of sister chromatid cohesion during meiosis I in C. elegans also function to inhibit centriole separation at meiosis II, thereby ensuring that the zygote inherits the appropriate complement of chromosomes and centrioles."
Traffic cops: Dyneins, kinesins and myosins are among the "motor proteins" that act like molecular trucks for transporting cargo around the cell on highways of actin or microtubules. Like human truckers, they face obstacles. What controls the traffic flow at intersections? Another paper on PNAS looks into the rules of the road in cellular "cargo transport" and finds right-of-way rules, suggesting a "high degree of regulation of motor activity to maintain transport in a given direction."
Electronic gatekeepers: The nuclear pore complex (and it is complex) is the gatekeeper to the nucleus. This paper in PNAS shows that electrostatic interactions help ferry the cargo through the gate: "The positive electrostatic potential facilitates the translocation of negatively charged particles."
Locksmiths: "To ensure that the genetic material is equally and accurately distributed to the two daughter cells during cell division, the DNA fibers must have an ordered structure and be closely packed," Science Daily reports. The article is accompanied by an intriguing image of molecular padlocks that hold DNA strands together in a process that "ensures order in the DNA packaging process."
Multitasking translator: "The ribosome has traditionally been viewed as the cell's molecular machine, automatically chugging along, synthesizing proteins the cell needs to carry out the functions of life," an article on PhysOrg says, preparing us for the surprise discovery that the ribosome is "More than a Machine." New research "reveals that the ribosome is not just an automatic molecular machine but instead also acts as a translational regulator."
Watchmakers: Another article on PhysOrg describes "Watching the cogwheels of the biological clock" in living cells. "Our master circadian clock resides in a small group of about 10,000 neurons in the brain, called the suprachiasmatic nucleus," the article begins. "However, similar clocks are ticking in nearly all cells of the body." How appropriate this was discovered by Swiss researchers, who "devised an elegant method to watch directly under the microscope how the clock's molecular 'cogwheels' govern the activity rhythms" of an essential protein.
Speaking of biological clocks brings to mind to some philosophical discussions in past centuries about watches and watchmakers. What if William Paley had known that living cells really are in many ways built like finely crafted timepieces? Here are more papers on biological clocks for those wishing to look into the subject further.

"The Circadian Clock Coordinates Ribosome Biogenesis" (PLoS Biology)
"Rhythmic Changes in Gene Activation Power the Circadian Clock" (PLoS Biology)
"Genome-Wide RNA Polymerase II Profiles and RNA Accumulation Reveal Kinetics of Transcription and Associated Epigenetic Changes During Diurnal Cycles" (PLoS Biology)
"Rhythmic Ca2+ Signaling: Keeping Time with MicroRNAs" (Current Biology): "Pacemaker cells are specialized cell types that drive biological rhythms like the heartbeat and intestinal peristalsis. What determines whether a cell functions as a pacemaker? Studies in Caenorhabditis elegans suggest that pacemaking activity may be controlled in part by microRNAs."
"Circadian Rhythms: An Electric Jolt to the Clock" (Current Biology): "The animal circadian pacemaker is composed of two transcriptional feedback loops, which regulate electrical activity in circadian neurons. Surprisingly, a new study reports that electrical activity can reprogram circadian transcription, and identifies CREB proteins as candidates for this reprograming."
Back in 1998, Bruce Alberts stated that the "biology of the future" was going to be the study of molecular machines (see here). He was correct; the journals can't get enough of the organic robots that carry on the functions of the cell. As scientists focus on the intricacies of molecular machines, they seem to find it less fruitful to talk about Darwin. With researchers thinking more and more in terms of engineering design, biology is moving along the right track.

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