Chu92
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Chu92
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ORGANELLE inside a protozoan was dragged to one end of photographs. The image seen at the far right shows the or-<br />
the cell using an optical tweezers, as shown in the first three ganelle after it was released.<br />
cused, counterpropagating beams of<br />
light [see "The Pressure of Laser Light,"<br />
by Arthur Ashkin, SCIENTIFIC AMERI-<br />
CAN, February 19721. But only much lat-<br />
er was it realized that if a single beam<br />
is focused tightly enough, the dipole<br />
force would suffice to overcome the<br />
scattering force that pushes the parti-<br />
cle in the direction that the laser beam<br />
is traveling.<br />
The great advantage of using a single<br />
beam is that it can be used as an optical<br />
tweezers to manipulate small particles.<br />
The optical tweezers can easily be inte-<br />
grated with a conventional microscope<br />
by introducing the laser light into the<br />
body of the scope and focusing it with<br />
the viewing objective. A sample placed<br />
on an ordinary microscope slide can be<br />
viewed and manipulated at the same<br />
time by moving the focused laser beam.<br />
One application of the optical tweez-<br />
ers, discovered by Dziedzic and Ash-<br />
kin, has captured the imagination of bi-<br />
ologists. They found that the tweezers<br />
can handle live bacteria and other or-<br />
ganisms without apparent damage. The<br />
ability to trap live organisms without<br />
harm is surprising, considering that the<br />
typical laser intensity at the focal point<br />
of the optical tweezers is about 10 mil-<br />
lion watts per square centimeter. It<br />
turns out that as long as the organism is<br />
very nearly transparent at the frequen-<br />
cy of the trapping light, it can be cooled<br />
effectively by the surrounding water.<br />
To be sure, if the laser intensity is too<br />
high, the creature can be "optocuted."<br />
M any<br />
applications have been<br />
found fop the optical tweezers.<br />
Ashkin showed that objects<br />
within a livm&cell can be manipulated<br />
without puncturing the cell wall. Steven<br />
M. Block and his colleagues at the Row-<br />
land Institute in Cambridge, Mass., and<br />
at Harvard University have studied the<br />
mechanical properties of bacterial fla-<br />
gella. Michael W. Bems and his co-work-<br />
prs at the University of California at<br />
Irvine have manipulated chromosomes<br />
inside a cell nucleus.<br />
Optical tweezers can be used to ex-'<br />
amine even smaller biological systems.<br />
My colleagues Robert Simmons, Jeff<br />
Finer, James A. Spudich and I are ap-<br />
plying the optical tweezers to study<br />
muscle contraction at the molecular lev-<br />
el. Related studies are being carried out<br />
by Block and also by Michael P. Sheetz<br />
of Duke University. One of the goals of<br />
this work is to measure the force gen-<br />
erated by a single myosin molecule<br />
pulling against an actin filament. We<br />
are probing this "molecular motor" by<br />
attaching a polystyrene sphere to an<br />
actin filament and using the optical<br />
tweezers to grab onto the bead. When<br />
the myosin head strokes against the<br />
actin filament, the motion is sensed by<br />
a photodiode at the viewing end of the<br />
microscope. A feedback circuit then di-<br />
rects the optical tweezers to pull against<br />
the myosin in order to counteract any<br />
motion. In this way, we have measured<br />
the strength of the myosin pull under<br />
tension.<br />
On an even smaller scale, Spudich,<br />
Steve Kron, Elizabeth Sundennan, Steve<br />
Quake and I are manipulating a single<br />
DNA molecule by attaching polystyrene<br />
spheres to the ends of a strand of DNA<br />
and holding the spheres with two opti-<br />
cal tweezers. We can observe the mole-<br />
cule as we pull on it by staining the<br />
DNA with dye molecules, illuminating<br />
the dye with green light from an argon<br />
laser and detecting the fluorescence<br />
with a sensitive video camera. In our<br />
first experiments we measured the elas-<br />
tic properties of DNA. The two ends<br />
were pulled apart until the molecule<br />
was stretched out straight to its full<br />
length, and then one of the ends was<br />
released. By studying how the molecule<br />
springs back, we can test basic theories<br />
of polymer physics far from the equi-<br />
librium state.<br />
The tweezers can also be used to<br />
prepare a single molecule for other ex-<br />
periments. By impaling the beads onto<br />
the microscope slide and increasing the<br />
laser power, we found that the bead can<br />
be "spot-weldedn to the slide, leaving<br />
the DNA in a stretched state. That tech-<br />
nique might be useful in preparing long<br />
strands of DNA for emnknatlm with<br />
state-of-the-art microscopes. Ultimate-<br />
ly, we hope to use these manipulation<br />
abilities to examine the motion of en-<br />
zymes along the DNA and to address .<br />
questions related to gene expression<br />
and repair. 4<br />
It has only been six years since work-<br />
ers have stopped atoms, captured them<br />
in optical molasses and made the first<br />
atom traps. Optical traps, to paraphrase<br />
a popular advertising slogan, have en-<br />
abled us to "reach out and touch" par-<br />
ticles in powerful new ways. We have<br />
shown that if we can "see" an atom or<br />
microscopic particle, we may be able to<br />
hold onto it regardless of intervening<br />
membranes. It has been a personal joy<br />
to see how esoteric conjectures in atom-<br />
ic physics have blossomed: the tech-<br />
niques and applications of laser cool-<br />
ing and trapping have gone well be-<br />
yond our dreams during those early<br />
days. We now have important new tools<br />
for physics, chemistry and biology. --<br />
FURTHER READING<br />
LASER SPECTROSCOPY OF TRAPPED<br />
ATOMIC IONS. Wayne M. Itano, J. C.<br />
Bergquist and D. J. Wineland in Science,<br />
Vol. 237, pages 612-617; August 7,<br />
1987.<br />
COOLING, STOPPING, AND TRAPPING<br />
ATOMS. William D. Phillips, Phillip L.<br />
Gould and Paul D. Lett in Science, Vol.<br />
239, pages 877-883; February 19,1988.<br />
NEW MECHANISMS FOR LASER COOLING.<br />
C. N. Cohen-Tannoua and W. D. Phil-<br />
Ups In Physics Today, Vol. 43, No. 10,<br />
pages 33-40; October 1990.<br />
LASER MANIPULATION OF ATOMS AND<br />
PARTICLES. Steven Chu in Science, Vol.<br />
253, pages 861-866; August 23.1991.