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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.

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