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07/01/92

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Physicists get a grip on atoms with laser tweezers, atomic fountains

STANFORD -- Using lasers to hold and move atoms and molecules with exquisite control, Stanford University physicist Steven Chu and his co-workers are making extremely precise measurements in physics and biology.

For example, they have used laser beams to chill sodium atoms to within a tiny fraction of a degree of absolute zero and create "atomic fountains" of slowly falling atoms. These fountains allow such precise measurement that the scientists can detect the gravitational change caused by moving four inches farther from the center of the earth.

The Stanford scientists believe that a portable gravity meter - suitcase-sized and a thousand times more accurate than current devices - might be available within a few years. With it, seismologists could monitor earth movements, oceanographers could measure sea-level changes, and geologists could locate buried oil deposits or monitor changes in the water table.

The scientists also use lasers as "optical tweezers" to grab and move individual biological molecules. Researchers can stretch out single molecules of DNA in water and observe them as they snap back elastically. They can also pin the stretched molecule down onto a microscope slide for observation.

Using these tweezers on muscle proteins, another group is measuring how much force a single molecule contributes to the muscle's contraction. This gives scientists the opportunity to understand for the first time how muscles contract, molecule by molecule.

"Six years ago, none of these applications were considered," Chu said. "No one dreamed we would ever control atoms or molecules this well."

Gravity measurement

The gravity measurement, which was part of Stanford graduate student Mark Kasevich's doctoral thesis, begins by using lasers to chill a few sodium atoms - about 10 million atoms, or 10 billionths of a billionth of an ounce - and trap them in a region of space only a millimeter in diameter.

At first glance, cooling atoms to temperatures near absolute zero by zapping them with laser beams seems unlikely, even contradictory. Yet a technique proposed by Stanford physicists Ted Hansch and Art Schawlow in 1975, and first demonstrated by Chu and his colleagues in 1985, does just that.

The technique, which Chu dubbed "optical molasses", makes high-tech use of the familiar effect known as the Doppler shift. Most people have noticed that a train horn sounds with a higher pitch - a higher frequency of sound waves - as it moves closer and changes to a lower pitch as it passes and moves away. That change is the Doppler shift.

Similarly, physicists know that the frequency of a light beam appears higher when an observer is approaching it than when the observer is moving away from it - again, a Doppler shift.

Optical molasses takes advantage of the fact that atoms absorb certain frequencies of light much better than other frequencies. A laser beam tuned to a light frequency just below one of those critical frequencies thus won't disturb most atoms. If an atom happens to be moving toward the laser source, however, the Doppler shift raises the laser's frequency slightly, making the atom more likely to absorb a photon of light energy. The impulse delivered to the atom during its collision with the photon slows the atom's motion.

By directing six laser beams at a single region of space - from above and below, front and back, left and right - Chu and his colleagues can slow any random motion of atoms in the target zone by hitting them with light energy from the opposite direction. Slowing atoms down is the same thing as cooling them, since the temperature of a collection of atoms is just a measure of their random motion.

The Stanford group trapped sodium atoms with lasers and magnetic fields, and used optical molasses to cool them to within 30 millionths of a degree of absolute zero. By adjusting the frequency of some laser beams, Kasevich lifted the atoms upward, gently lofting them into a free-falling arc, or "fountain," that lasted for nearly a second.

"To have a free atom in your hands for a full second - it's a new regime in atomic physics," Kasevich said.

Heisenberg's famous Uncertainty Principle implies that the less time you have to make a measurement, at least at the atomic level, the less accurate it will be. Normal room-temperature atoms travel at supersonic speeds, so they're difficult to follow long enough to measure accurately. The atoms in an atomic fountain, on the other hand, hit a top speed of only about 2 meters per second - roughly the speed of a ball dropped onto a table from eight inches up - and thus allow extremely accurate measurements.

Kasevich determined the speed of the falling atoms by measuring the size of their Doppler shift as they fell toward yet another laser. Using a highly accurate atomic clock to time their fall, he could calculate gravity's acceleration with great precision.

"The philosophy of my lab is to turn every measurement we can into a frequency measurement. Any time you can do that, you've won big," Chu said, since frequency can be measured much more precisely than any other quantity.

"Instead of measuring the distance an atom falls in a certain amount of time, our atomic gravity meter measures the change in velocity during a given time by measuring the Doppler shift of a very well-known atomic frequency."

Kasevich so far has measured gravity's tug to a precision of three parts in 100 million. He and Chu expect to push that precision still further in the near future, to one part in 10 billion, which would make their technique almost a thousand times more accurate than any others, Chu said.

Through Stanford University, Kasevich and Chu have applied for a patent on the atomic gravity meter. A durable, suitcase-sized portable device might be possible within a few years, Chu said.

A portable gravity meter with an accuracy of one part in 10 billion could measure change in elevation to the nearest third of a millimeter, Kasevich said, since the pull of gravity diminishes as one moves farther from the center of the earth. Such equipment would give seismologists and oceanographers easy and accurate measurements of land and sea changes.

In addition, geologists could detect changes in the composition of buried rock formations by measuring gravitational differences, since gravity would be a bit stronger over higher-density formations. This might provide a handy way to search for underground oil deposits or monitor changes in the water table, Chu said.

"We're talking to geophysicists now. We've invented something, but we're not experts in the uses of it, so we're talking to others and letting them know it's available," Chu said.

Laser tweezers

The second group of Stanford researchers uses laser beams at a scale only slightly larger - to grab and manipulate the individual protein molecules that cause muscles to contract.

"The goal is to discover how proteins act as motors - how they convert chemical energy into mechanical work. It's kind of the Holy Grail of biophysics," said Jeff Finer, a graduate student of biochemistry Professor Jim Spudich's. Finer is doing the work with Chu, research associate Hans Warrick and Robert Simmons, an English researcher now on leave at Stanford.

Each muscle cell contains thousands of muscle fibers arranged parallel to one another like a package of dry spaghetti. Within each fiber, bundles of two kinds of protein molecules - called actin and myosin - alternate in bands, overlapping one another like hands with long, loosely interlaced fingers. When the muscle contracts, the actin molecules slide along the myosins, interlacing further and bringing the "hands" closer together. This shortens the muscle. When the muscle stretches, the hands separate again, with the actin molecules sliding back and reducing their overlap with the myosins.

Scientists theorize that the sliding motion of actin molecules over myosins is controlled by dozens of tiny "heads," looking much like the heads on golf clubs, that stick out from the side of each myosin molecule. The heads attach to neighboring actin molecules wherever they overlap.

According to the theory, when the muscle contracts, the myosin heads pivot like toggle switches, pulling the actin molecule along. Then the heads release the actin, pivot back to their original position, and repeat the process. In this way, the myosin molecule inches the actin, caterpillar fashion, along its length.

"This model of muscle contraction has been around for 20- some years, but there's no direct evidence of it," Finer said, largely because scientists have been unable to measure the tiny motions and minuscule forces produced by each myosin head.

The Stanford researchers may be about to change all that. Using Chu's optical tweezers, Finer has developed a way to pin down individual actin molecules and track their movements precisely. Soon, he hopes to use this technique to measure the force of a single myosin head's pull.

Since protein molecules are too small to grab directly with optical tweezers, Finer attached handles - plastic beads about 1/25,000 of an inch in diameter - to each end of the actin molecule.

The tweezers' strongly-focused laser beam creates an intense electric field at its focus, slightly redistributing the bead's electric charges. This draws the bead to the laser beam in much the same way that static electricity draws a piece of tissue paper to the tooth of a comb.

"An actin molecule is like a floppy rope," Finer said.

By grabbing each end of the rope and pulling it taut, he can move the actin molecule precisely where he wants it. He is gradually refining his ability to place the actin next to exactly one myosin head to measure the force of its tug.

Muscle physiologists expect that force to be roughly 3 trillionths of an ounce - not an easy pull to measure with a conventional scale. Fortunately, laser traps provide a way to measure forces like this, as well.

The electric field of the laser tends to hold the bead in the dead center of the beam. Pulling the bead away from the center of the laser beam requires force, and the farther it's pulled away, the greater the force.

Finer can detect these tiny motions - as little as 1/1,000 of the bead's diameter - by shining a light on the bead and measuring changes in the way the bead deflects the light beam.

"Our goal is to have the data as simple as possible," Finer said. "Before this, there hasn't been a prayer of making direct measurements on single events."

Finer thinks he'll have such measurements "any day now." Once he's cracked the actin-myosin problem, he hopes to focus his tweezers on other molecular motors found in cells, such as the motor the cell uses to move chromosomes during cell division.

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