molecules

MAKING

motors INTO

HUDDLED IN THE RUINS OF

a house in southwestern London, the protagonist of
The War of the Worlds marveled at the strangeness of
Martian technology:
Of their appliances, perhaps nothing is more won-
derful to a man than the curious fact that what is the
dominant feature of almost all human devices in
mechanism is absent— the wheel is absent.

An advanced technology can do away with things we

Molecular turmoil, quantum
regard as absolutely essential. Just that is happening
now in a blossoming field at the intersection of physics,
craziness: microscopic
chemistry and biology: the study and construction of
devices that serve as motors and pumps on the molec-
machines must operate in
ular scale. These mechanisms generally lack rotors, ar-
matures and all the other trappings of conventional en-
a world gone mad. But if
gines, but that is the least of their oddities. In an ordi-
nary motor, energy is used to cause motion. In these
you can’t beat the chaos,
motors, energy is used to cause a cessation of motion.
Although they seem rather like an example of alien tech-
why not exploit it?
nology, they are the most common type of motor on our
planet, the basis of the inner workings of all living cells.
Our physical intuition, formed by everyday obser-
vation of large machines, fails when we consider the
BY R. DEAN ASTUMIAN
world of the small. It is a capricious world, ruled by
thermal and quantum fluctuations. For molecules, mov-
ing deterministically is like trying to walk in a hurricane:
the forces propelling a particle along the desired path
are puny in comparison to the random forces exerted
by the environment. Yet cells thrive. They ferry mate-
rials, they pump ions, they build proteins, they move
from here to there. They make order out of anarchy.

SCIENTIFIC AMERICAN 57
 Over the past several years, researchers Usually when you park your car at the would be agonizingly slow, however, be-
have finally begun to understand how. foot of a hill, turn off the engine and re- cause only a small fraction of the hail-
The basic insight, loosely described as the lease the emergency brake, the car will stones—those with enough momentum to
Brownian ratchet principle, is that ran- not start climbing the hill. But imagine overcome the force exerted on the ratchet
dom noise can be put to good use. The this scenario. Hundreds of hailstones by the spring—would have any effect.
trick is to rectify the noise, to filter out the strike the car every second, hitting all A better alternative is to skew the teeth
randomness you do not want so that you sides at random. Each one transfers a in the opposite direction and substitute the
are left with what you do want. This prin- small amount of momentum to move the spring-loaded pawl with a piston activat-
ciple resembles the phenomenon known car a tiny distance forward or backward. ed by the brake pedal. When the brake is
as stochastic synchronization, whereby On average, the momentum transferred off, the piston is disengaged, and the car is
increasing the noise in a communications to the car is zero, but in any time inter- free to lurch back and forth. When the dri-
channel can actually make it easier to val the car will move a little more in one ver pushes the brake pedal, the piston en-
transmit a signal [see “The Benefits of direction than in the other. gages and locks the gear (and car) in place.
Background Noise,” by Frank Moss and You can take advantage of these ran- This modified ratchet does away with
Kurt Wiesenfeld; Scientific American, dom pushes in a very simple way. Put a the need for careful measurement and in-
August 1995]. brick behind the rear wheel to prevent telligent intervention. All the driver has
Using the techniques of chemistry, re- the car from rolling backward and wait to do is sit in the car and pump the brake.
searchers have been designing miniature until a hailstone pushes it forward. If you Because of the skewed gear teeth, a few
motors and devices that can manipulate do nothing, the car will soon roll back, extra hailstones striking from behind are
molecules one at a time. These tiny ma- but if you swiftly move the brick, you can sufficient to move the car forward far
chines imitate what protein motors and trap the car in its new position. By con- enough to advance the gear by one tooth,
pumps do in living cells— convert chemi- tinuing this process— moving the brick whereas a larger number of hailstones
cal energy into mechanical work with al- each time the car lurches forward— you from the front are necessary to push it
most 100 percent efficiency— and could can drive down the street, even up a hill. backward by one tooth. This asymmetry
carry out such tasks as molecular assem- It takes a keen eye and quick wit to ensures that the car moves forward even
bly, fine sifting, low-energy-consumption move a brick under a heaving car in the if the brake is engaged and disengaged
computation and semiconductor quality middle of a violent hailstorm. Fortunate- randomly. The beauty of the system is
control. They may be the first step in ly, the same effect can be achieved simply that it requires no synchronization—
turning the science fiction of nanotech- by replacing the standard brake with a none of the careful timing required in an
nology, the dream of atom-by-atom con- ratchet— a device that allows motion in ordinary engine.
trol of matter, into science fact. only one direction. A ratchet consists of a Averaged over time, the hailstones
gear with asymmetric teeth and a pawl, a exert no net force on the car. The vehicle
Braking into Motion little arm that jams the gear and prevents acquires its forward motion from the ap-
E V E N A F R E A K H A I L S T O R M does not it from turning backward. In a turnstile or plication of the brake, which forces the
come close to the tempestuous bombard- ratchet wrench, the pawl is spring-loaded. piston down onto the gently sloping face
ment that is routine in the molecular Such a simple ratchet mechanism would of the lopsided teeth. Take away any
world, but the effects can be analogous. keep the car moving forward. Progress component— the asymmetry of the ratch-
et teeth, the jittering caused by the hail-
stones or the external energy supplied by
Overview / Motors from Molecules pumping the brake— and the mechanism
would fail.
To make a molecular motor, it isn’t enough just to make a miniature version of Needless to say, such a contrivance is
an ordinary motor. Researchers have had to rethink the very premises on which quite unrealistic for a real car. A back-of-
a motor operates. envelope calculation shows that a rea-
■ In ordinary motors, an energy input causes motion. In molecular motors, an sonable pumping rate could impart a ve-
energy input restrains motion. By selectively stopping the motions it doesn’t locity of no more than a kilometer per
ILLUSTRATION ON PAGE 56: PHILIP HOWE

want and letting through the ones it does— using a ratcheting mechanism hour, about a tenth of the car’s body
akin to a ratchet wrench— the motor turns momentum from random length per second. The maximum force
environmental influences into organized motion. on the car would be one millionth the
■ Ratchets sound like they get something for nothing, but the second law gravitational force, so at best the car
of thermodynamics wouldn’t look kindly on that. Physicist Richard Feynman could climb a very gradual slope.
explained how these systems are completely kosher. But if the car is very small— say, the
■ Such motors make many of the dreams of nanotechnology possible. They also size of a large molecule— and immersed
explain how living cells function amid the chaos of the microworld. in water, the mechanism is much more
effective [see box on page 60]. The mass

58 SCIENTIFIC AMERICAN JULY 2001

 UPHILL BATTLE
DRIVING UPHILL WITHOUT AN ENGINE is an apt metaphor for understanding molecular
motors. It sounds impossible but can happen if a car is equipped with a special ratchet
brake and is bombarded by hailstones. In terms of potential energy, the hill can be
represented by a straight line and the brake (when applied) by a lopsided sawtooth.

60%
Potential
Energy

39%

Position
When the brake is on, the car is forced When the brake is off, hailstones buffet
down into the notch of the sawtooth. It is the car, making it jiggle back and forth
unlikely that a hailstone would push the randomly. The probability of reaching a
car out of this locked position. (If one certain position can be calculated from
did, the car would actually tend to move the slope of the hill and the amount of
backward— that is, the path of least time available. Despite the downhill bias, Reapplying the brake pushes the car back
resistance for the ratchet.) the car is more likely to move past the to where it started (for this example, with
position of the peak to the right than the 60% probability), forward one notch (39%)
peak to the left (dashed lines). or back (1%; not shown).

ratio of a water molecule and a small principle applies to games of chance. wheel from going backward, molecular
protein is about the same as the mass ra- Switching between two games, each a collisions would cause an irregular but re-
tio of a hailstone and a car. The differ- losing proposition, can turn the odds in lentless rotation of the wheel [see illustra-
ence is that water molecules hit the pro- your favor [see box on page 62]. tion on page 61]. The result: a perpetual-
tein many billion times a second. These motion machine of the second kind—that
collisions produce the well-known jitter- Long Arm of the Second Law is, one that defies the second law. (The de-
ing called Brownian motion. What is not A P H Y S I C I S T ’ S F I R S T reaction is that vice does not claim to manufacture ener-
so well known is that a Lilliputian ratch- ratchets might break the second law of gy out of nothing, so it does not violate
et could use Brownian motion to turn di- thermodynamics, whereby it is impossi- the first law of thermodynamics, the law
rectionless energy into directed motion. ble to convert random thermal fluctua- of conservation of energy.)
A small protein could reach a velocity of tions into mechanical work. In his famous As Feynman showed, however, the de-
one micron (more than 10 times its size) Lectures on Physics, Richard Feynman vice cannot work without an outside en-
a second— the equivalent of 100 kilome- analyzed a ratchet attached to a paddle ergy source. The pawl must be attached
ters an hour for a car. The ratchet mech- wheel. If the ratchet could prevent the to the ratchet by a spring, which itself is
anism could overcome a force of up to 10
piconewtons, nearly a million times the THE AUTHOR
force of gravity on a molecule. R. DEAN ASTUMIAN is a physics professor at the University of Maine, having recently moved from
It is amazing but true that two ran- the University of Chicago, where he taught biophysics. He is the author of more than 50 articles
dom processes can combine to produce a on molecular motors and pumps, the recipient of the 1987 Galvani prize of the Bioelectrochemical
PHILIP HOWE

nonrandom effect. Physicist Juan M. R. Society and a fellow of the American Physical Society. His other scientific interests include the sta-
Parrondo of Complutensian University tistical mechanics of signal transduction by biological cells. He is an avid pianist and hiker, enjoy-
in Madrid recently showed that the same ing the natural beauty of Maine with his wife, son and daughter.

www.sciam.com SCIENTIFIC AMERICAN 59

vulnerable to thermal noise. Occasional- car is forced into the locked position. In phosgene gas. A hydroxyalkyl group was
ly noise causes the spring to contract, lift- this way, these systems comply with the attached to the pawl and an amino group
ing the pawl and prematurely disengaging second law. to one vane of the paddle wheel. Togeth-
the mechanism. Because of the asymme- Although large thermal gradients are er they served as a brake. Whenever the
try of the gear teeth, the ratchet will most rare at the molecular level, other forms of vane approached the pawl, the groups
likely slip back a notch. If the paddle disequilibrium are quite common. Three (primed by the phosgene) reacted and pre-
wheel and pawl are at the same tempera- years ago organic chemist T. Ross Kelly vented any further counterclockwise rota-
ture, the tendencies to move forward (be- and his colleagues at Boston College elab- tion. The net effect was that most of the
cause of molecular collisions) and to orated on this point with a clever experi- paddle wheels rotated clockwise. This sys-
move backward (because of the unreli- ment. They synthesized Feynman’s ratch- tem is not a true molecular motor— if the
able spring) exactly cancel. Despite su- et from triptycene, a Y-shaped organic brake were released and reapplied, the
perficial appearances, a ratchet system in molecule that serves as the paddle wheel, wheel would tend to return to its starting
thermal equilibrium will not rotate. and helicene, a G-shaped molecule that point— but it does demonstrate the con-
This restriction does not apply when acts as the pawl and spring. Because the cept. Other groups have achieved contin-
the system is out of thermal equilibrium. helicene has a bend in it, it is easier to turn uous rotation using different ratchet mech-
If the paddle wheel is hotter than the the paddle wheel clockwise than counter- anisms. A team headed by Ben L. Feringa
spring, the ratchet rotates counterclock- clockwise. Despite this asymmetry, NMR of the University of Groningen, for in-
wise, as intuition would suggest. If the spectroscopy showed that the frequencies stance, drives a molecular motor with light.
spring is hotter, the ratchet rotates clock- of clockwise and counterclockwise turns
wise— a motion that ratchets usually pre- were exactly equal, as Feynman predict- Pump the Brake
vent. Any departure from equilibrium al- ed [see “Taming Maxwell’s Demon,” by R E C E N T E X P E R I M E N T S suggest that
lows for ratchet-driven motion. Whatev- George Musser; Scientific American, at least some biological engines work by
er creates the disequilibrium provides News and Analysis, February 1999]. similar means. One example is the ion
energy to the system. In the case of the Kelly’s group then incorporated a non- pump, a protein that pushes electrically
car, the energy comes from the foot on the equilibrium chemical process: the hydro- charged particles through a cell membrane.
brake. The energy dissipates to heat as the lysis, or water-driven decomposition, of Ions naturally flow from higher to lower

BRAKE LIGHT
BIZARRE THOUGH IT MAY SEEM, the brake-driven car is exactly analogous to
a rudimentary molecular motor. In one elegant experiment seven years PLASTIC BEAD
ago, Albert J. Libchaber, a physicist then at Princeton University, and his
colleagues used a micron-size plastic bead floating in a beaker of water as
the “car.” They manipulated the bead using light beams; the subtle
pressure of light refracted through the bead pushed it toward regions
where the light intensity was strongest. One light beam created a circle of
light that generally confined the bead: the “road.” Superimposed on the
road was a second beam that could be turned on or off: the “brake.” The
brake beam set up an alternating series of bright and dark regions, in which
the positions of maximum and minimum intensity were not evenly spaced
(right). Moving clockwise from a maximum, it was a short distance to the
next minimum; moving counterclockwise, a long distance. This asymmetry
is analogous to the skew of the gear teeth in a mechanical ratchet.
With the brake beam on, the bead moved in the direction of increasing
intensity. On reaching the next maximum, it remained there as long as the
brake was applied. With the brake beam off, the bead randomly lurched
around the circle. If it managed to drift past a minimum, then reapplying the
brake pushed it to the next maximum. Because of the asymmetry, the bead
was more likely to move clockwise. The net velocity depended on how often
the brake beam was turned on and off. As the frequency increased, so did the
Intensity
Light

velocity, until it reached the point where Brownian motion could not keep up.
As with the car example, this system required no measurement, no
choreography and no application of intelligence during operation. It worked
PHILIP HOWE

even if the brake beam was turned on and off at random. Position on Circle (measured clockwise)

60 SCIENTIFIC AMERICAN JULY 2001

 Unlike an ordinary engine, a Brownian motor
REQUIRES NO MEASUREMENT and no choreography.
electrochemical potential, but these side. In the mid-1980s this ratchet picture nesin. Release of the hydrolysis products
pumps can drive ions in the opposite di- was corroborated by Tian Y. Tsong, then returns the potential to the sawtooth
rection, maintaining the electrochemical at Johns Hopkins University, me, and our shape, which, depending on how far the
gradients essential for life. colleagues. We applied an alternating kinesin has drifted, can push the molecule
The ion pump seems to be based on a electric field to an ion pump and observed forward.
simpler device, the ion channel. An ion it driving ions up an electrochemical gra- This Brownian model of how kinesin
channel is a biological rectifier: it allows dient, even without hydrolyzing ATP. moves differs radically from the tradi-
electric current to flow in one direction Another example is kinesin, a molecu- tional one, in which the shape of the mol-
only. A typical channel is a funnel-shaped lar forklift that transports proteins with- ecule played the central role. The idea was
protein about 10 nanometers long. Ions in the cell. Kinesin consists of two loosely that the two domains, acting like arms, let
can move from the mouth of the funnel to attached domains and moves along a go of the microtubule one at a time and
the tip, but not the other way. Turning this track called a microtubule, made of many swing forward— as though they were
rectifier into a pump requires some mech- individual molecules of the protein tubu- moving along monkey bars in a play-
anism to modulate the size of the mouth lin, each about 10 nanometers long. The ground. A clear prediction of this theory
and the strength of the interaction of an electric potential between the kinesin and was that if one domain is removed, the re-
ion within the channel. The shape of the the microtubule usually has a sawtooth sulting molecule should not be able to
channel is well suited to this type of mod- pattern, with energy barriers preventing move along the microtubule. In 1998 Ya-
ification, because it acts like a lever: a small the motion of kinesin from one tubulin sushi Okada and Nobutaka Hirokawa of
displacement of atoms near the tip of the molecule to the next. In the Brownian the University of Tokyo replaced one of
funnel can result in a large change at the model, hydrolysis of an ATP molecule the domains with a charged loop of
mouth. By making the mouth open and changes this potential to a flat shape and amino acids, so that the molecule had a
close cyclically, the pump can move ions allows random collisions to jostle the ki- different shape but nearly the same bind-
from the tip of the funnel out the base—
just as pumping the car brake caused the
gear to turn in the opposite direction from SPRING
what one would have expected.
The hydrolysis of adenosine triphos-
phate (ATP), the fuel used by cells, pro-
vides just the mechanism required to turn PAWL
a channel into a pump. In a simplified de-
scription, the pump has two possible
states. In the first state, the mouth is open
to the inside of the cell and ions interact
strongly with the interior of the channel.
In the second, the mouth is closed to the
inside and ions interact weakly with the
interior. The binding of ATP favors the
first state, and the release of the hydroly-
sis products favors the second. The pro-
cess is analogous to the operation of a
canal lock but with a crucial difference:
it requires no control mechanism to syn-
chronize the hydrolysis with the ion mo-
tion. It is enough to cycle randomly be-
PHILIP HOWE AND KEVIN RING

tween two states of the protein. When the RATCHET MECHANISM studied by physicist Richard Feynman shows how random bombardment
gate to the inside is open and the chan- can bring about nonrandom motion. The gas molecules hitting the propeller cause the gear to turn,
nel’s energy level is low, an ion naturally but which way does it go? If the spring-loaded pawl— the arm that jams the gear— works correctly,
enters the channel from the inside. When the gear can only turn counterclockwise. But when thermal noise causes the spring to release and
the gate to the inside is closed and the en- reengage, the gear tends to turn clockwise because of the asymmetry of the gear teeth. This effect
ergy level is high, the ion flows to the out- dominates whenever more heat is applied to the spring than to the gas.

www.sciam.com SCIENTIFIC AMERICAN 61

ing energy. This molecule moved rough- unzip DNA, transport proteins across our ian motion or fight against it, and the for-
ly as fast as the normal two-armed ki- cell membranes, and break down proteins mer seems to be the preferable choice.
nesin, in support of the Brownian model. when they are no longer needed. In some The Brownian ratchet principle gives
Brownian motion may also play a role cases, the evidence is equivocal, and re- scientists and engineers a whole new way
in the biomolecular motors that make up searchers still debate what is going on. to manipulate matter on a small scale.
our muscles [see box on page 64], assem- But one thing is clear: any microscopic One of the first applications has been to
ble our proteins, synthesize ATP, zip and machine must either work with Brown- separate particles by weight. This process

GAMBLER’S PARADOX
THE APPARENT PARADOX of Brownian ratchets— that flip-flopping odds for each game represent the overall driving force, and the
between two states of a system, each of which independently coin flip acts as the random input of energy. The game has an
loses energy, can allow a system to gain energy— also applies to asymmetry: according to the first set of rules, the piece tends to
games of chance. Last year physicist Juan M. R. Parrondo of spend a longer number on a black square than on a white one, and
Complutensian University in Madrid and engineer Derek Abbott of vice versa for the second set of rules. The coin flip erases this
the University of Adelaide in Australia came up with a pair of coin asymmetry. (Sadly, the same trick will not work for two standard
games that illustrate the paradox. If you play either game by casino games, which lack the type of asymmetry that a simple
itself, you tend to lose, but if you randomly switch between them, coin toss would eliminate.)
you tend to win. The trick is that even a losing game lets you win A similar reversal of fortune occurs in many areas of life;
occasionally. By switching games, you lock in those winnings statisticians refer to it as Simpson’s paradox. It can happen
before the inevitable loss takes them away. whenever the probabilities of some events are constant while
Although Parrondo and Abbott’s game uses biased coins, others fluctuate. In the above example, the probability of a
other examples require only a standard (unbiased) coin and a fair backward move is nearly constant while that of a forward move
(not loaded) pair of dice. For instance, consider a game that fluctuates depending on the outcome of the coin flip. The paradox
combines craps with checkers. You play it by moving a piece has led researchers to draw incorrect conclusions from merged
along part of a checkerboard. The object is to start in the middle data sets and can lure the naive into subtle investment and
and get to the right side before the left side [below]. The player insurance scams.
moves the piece either forward or backward by rolling a pair of Consider a disaster insurance pool that covers both hurricanes
dice and consulting a table of craps-like rules. If the player uses (which tend to strike in late summer and fall) and earthquakes
either of the two sets of rules given here— which are identical (which can strike year-round). In this simple example, both
except for reversing the roles of black and white— he or she tends disasters occur at the same average rate. Floridians and
to lose. The relative probability of winning equals the number of Californians pay a monthly premium, and when disaster strikes,
ways to move forward from white to black times the number of the victims receive a certain fraction of whatever money is in the
ways to move forward from black to white (8 × 2). Losing involves fund at that time. Wily Floridians might plead that because their
moving backward twice (5 × 4). For either set of rules, the player businesses are highly seasonal, they should pay less in the fall
can expect only 80 wins for every 100 losses. and winter and, to make up for it, more in the spring and summer.
But suppose we allow a coin flip before each move. For heads, Would that be fair? Surprisingly, no. The Floridians’ approach would
the player makes a move according to the first set; for tails, the make the fund larger during hurricane season, so they would tend
player uses the second set. Now the probability of winning is the to get larger payouts than the Californians. Using different rules,
product of the average number of forward moves: (8 + 2)/2 × clever Californians could tilt the game in their favor. — R.D.A.
(8 + 2)/2 = 25. The probability of losing depends on the product of
the average number of backward moves: (4 + 5)/2 × (4 + 5)/2 = CRAPS-LIKE GAME involves moving a checkers piece depending on the
20.25. Thus, the player can expect to win 100 times for every 81 roll of two dice. The sum on the dice determines the direction of
times he or she loses. motion. In each of the two rule sets, the piece usually moves backward,
In this game the dice simulate thermal noise, the unfavorable but randomly switching between the sets reverses the direction.

RULE SET 1 RULE SET 2

WHITE BLACK WHITE BLACK
LOSE

WIN

FORWARD 7, 11 11 FORWARD 11 7, 11
BACKWARD 2, 3, 12 2, 4, 12 BACKWARD 2, 4, 12 2, 3, 12
PHILIP HOWE

62 SCIENTIFIC AMERICAN JULY 2001

 Using a QUANTUM RATCHET, researchers could gain
precise control of individual electrons.
is a microscopic version of panning for ones, they had more time to drift side- and his colleagues at the University of
gold. When you subject particles to ran- ways while in the space between obsta- Augsburg in Germany made the tantaliz-
dom fluctuations— either by shaking a cles. The asymmetric barriers made it eas- ing suggestion that quantum effects— in-
tray or by subjecting them to Brownian ier for them to drift in one direction rather terference between electron wave func-
motion—the heavier ones move at a slow- than simply spread out. By the time the tions, quantization of energy levels, elec-
er speed. The first steps toward building charged molecules had reached the other tron tunneling through barriers— could
Brownian sieves were taken nine years ago side of the slide, they had sorted them- provide another randomizing force. These
by physicists Armand Ajdari of the Paris selves into different groups by charge. effects would take over from Brownian
School of Industrial Physics and Chem- motion at the lowest temperatures and
istry and Jacques Prost of the Curie Insti- A Quantum Leap smallest scales. Using a quantum ratchet,
tute. Recently Joel S. Bader and his col- I T W A S O N L Y a matter of time before researchers could gain precise control of
leagues at the biotech company Curagen ratchets found their way into the quan- individual electrons without having to ex-
in New Haven, Conn., built a device to tum world. Four years ago Peter Hänggi ert comparably precise manipulation of
sort DNA molecules. Their approach electric fields.
promises greater precision and selectivity QUANTUM DOT Since that time, Charles M. Marcus,
than standard sorting techniques such as then at Stanford, and his colleagues have
electrophoresis, centrifuge and distillation. made an electron pump from a quantum
In all of the above ratchet examples, dot, which acts as a tunnel between two
the ratchet electric field is either on or off. larger reservoirs of electrons and can be
In 1996, however, Martin Bier and I (both closed off by electrostatic gates. By cycling
of us then at the University of Chicago) the voltage on the dot and on the gates,
suggested using three states: positive, neg- Marcus’s team pushed electrons between
ative or off. By switching among these the reservoirs one by one. Because their
states, a Brownian sieve could make heavy ION CHANNEL system was always near equilibrium, the
particles move one way and light particles process was reversible, allowing the ener-
the other way. Particles could be continu- gy usage to be made arbitrarily small.
OUTSIDE OF CELL

INSIDE OF CELL

ously fed into the middle of the device, col- Two years ago Imre Derényi and I
lected at either end, fed into another device (both of us then at Chicago) designed a
tuned to a different mass, and so on, with similar mechanism in which the voltage
ever better separation at each stage. Such changes would be abrupt and random.
devices could sort not just by mass but Such a system would be intrinsically irre-
also by size or electric charge. Theorists at versible— the direction an electron is
Princeton, Chicago, the Massachusetts In- pumped does not depend on the order in
stitute of Technology and the University which the steps are carried out— and
RODERICK M A C KINNON Rockefeller University IN DECLAN A. DOYLE ET AL.,

Potential Energy

of Ottawa have since extended this idea hence more wasteful. But it would have
into two dimensions. advantages, especially as a model of irre-
HEINER LINKE University of New South Wales (quantum dot);

Two years ago Alexander van Oude- versible chemical reactions, such as those
naarden and Steven G. Boxer, both then used to drive the ion pump. Other poten-
SCIENCE, VOL. 280; 1998, © 1998 AAAS (ion channel)

at Stanford University, built a working tial applications include electron pumps

2-D sieve. They used electron-beam lith- Position in molecular computers and amplification
ography to pattern a glass slide with an TWO RATCHETS differ in detail but may work in of signals along molecule-scale wires.
array of asymmetric barriers 25 nanome- basically the same way. The micron-size Meanwhile Heiner Linke, formerly at
ters high. They filled this tiny maze with a triangular quantum dot, etched onto a silicon Lund University in Sweden, and his col-
fluid of electrically neutral phospholipid wafer, is a diode— a device that turns leagues have used triangular quantum
molecules, mixed in some phospholipids alternating current into direct current. The ion dots. The triangles acted as ratchets be-
with various electric charges and applied channel— a protein molecule shown here as cause it was harder for electrons to squeeze
an electric field. The field pulled the a cutaway surface— is a biological version of a through the vertex. When an oscillating
charged molecules through the obstacle diode, a hundredth the size of the dot. The voltage modulated this built-in bias, a net
course. Because singly charged molecules potential energy profile is thought to be the current flowed— even though the average
moved more slowly than doubly charged same for both devices. voltage was zero. Varying the temperature

www.sciam.com SCIENTIFIC AMERICAN 63

MUSCLING IN by Toshio Yanagida

ONE OF THE UNEXPECTED SUCCESSES of the theory of Brownian molecule of myosin cleaves a molecule of ATP, gains energy and
ratchets has been a new explanation for muscle contraction. changes shape. In the process, it pulls an actin filament along by
Biomedical researchers have long known that flexing a muscle a single step— rather like climbing a ladder. This model is still
causes two kinds of filaments, made of proteins called myosin popular because it posits that muscle contraction is, like the
and actin, to slide along each other. The molecules convert operation of ordinary motors, an easy-to-understand,
chemical energy— in the form of adenosine triphosphate (ATP)— deterministic process. The problem, however, is that an ordinary
into kinetic energy with an efficiency of about 50 percent. This motor should get less, not more, efficient as it is shrunk.
process works even if the chemical energy is barely more To resolve this contradiction, we developed new technologies
powerful than the noise represented by ambient heat. In to manipulate molecules and to identify tiny movements and
contrast, artificial machines such as electric motors and car forces: fluorescent labeling, special short-range lighting called an
engines operate at energies much higher than the thermal noise. evanescent field, laser trapping, and scanning probes. These
How can molecular motors be so efficient? efforts finally bore fruit four years ago.
A long-held theory says that muscles contract when a We discovered that myosin and actin do not, in fact, behave
deterministically. The myosin hopped stochastically in steps
from 5.5 to 27.5 nanometers long. Each step was a multiple of 5.5
nanometers, equal to the separation of actin molecules in a
MYOSIN filament. A step, no matter how long, corresponded to the
HEAD
consumption of a single ATP molecule. Sometimes the myosin
even jumped backward rather than forward. These findings are
hard to account for with the traditional model but are quite
consistent with a Brownian ratchet. Although many questions
remain— for example, how exactly does ATP transform the
random Brownian motion into forward movement?— the basic
ACTIN FILAMENT picture explains how muscle contractions can be so efficient:
rather than trying to overcome noise, they exploit it.
MOTION OF MYOSIN, crucial to the functioning of animal muscle,

PHILIP HOWE
shows not just forward but also backward and multiple jumps— as Toshio Yanagida, one of the leading experimentalists in biophysics,
expected if random molecular bombardment plays a major role. is a professor at Osaka University Graduate School of Medicine.

regulated the direction of the current. At tric repulsion, which pushes them apart. istry rather than of mechanical engineer-
high temperatures the device functioned as The concepts filtered into biology as a pos- ing, we may have micron-size factories as-
a thermal ratchet: the electrons tended to sible explanation of biological transport sembling nanometer-size parts for motors
flow out of the vertex of the triangles be- driven by nonequilibrium chemical reac- to perform microscopic surgery; pumps to
cause once through the vertex it was hard- tions. Nowadays biological systems are in- rid the factories (and maybe our cells) of
er for them to go back. At low tempera- spiring the design of chemically synthe- unwanted waste products; and transistors
tures it turned into a quantum ratchet: sized molecular motors and pumps, so- for molecular computers to control these
electrons flowed out of the base of the tri- phisticated sieves and quantum rectifiers. and other processes. Just as in The War of
angles because the width of the energy The flow of ideas has reversed, and the the Worlds, which ends with the Martians
barrier was smaller in that direction, there- progress is anything but random. In the being felled by humble germs, the small
by making tunneling faster. In addition to near future, using the principles of chem- may end up conquering the large.
their applications in electronics, quantum
ratchets could be used to damp the current MORE TO E XPLORE
vortices that develop in superconductors, The Laws of the Game. Manfred Eigen and Ruthild Winkler. Princeton University Press, 1993.
thus resolving a major problem for mag- The Second Law. P. W. Atkins. W. H. Freeman and Company, 1994.
nets and superconducting wires. Thermodynamics and Kinetics of a Brownian Motor. R. Dean Astumian in Science, Vol. 276,
These ideas bring us full circle. A cen- pages 917–922; May 9, 1997.
A Single Myosin Head Moves along an Actin Filament with Regular Steps of 5.3 Nanometres. K. Kitamura,
tury ago Brownian motion helped tremen-
M. Tokunaga, A. H. Iwane and T. Yanagida in Nature, Vol. 397, pages 129–134; January 14, 1999.
dously in demonstrating the existence of Warmth Disperses and Time Passes: A History of Heat. Hans Christian Von Baeyer.
atoms. It also explained chemical reaction Random House, 1999.
rates as a balance between thermal noise, Playing Both Sides. Erica Klarreich in The Sciences, Vol. 41, No. 1, pages 25–29; January/February 2001.
which brings molecules together, and elec- For a simulation of a basic ratchet, visit monet.physik.unibas.ch/~elmer/bm

64 SCIENTIFIC AMERICAN JULY 2001