Life's Ratchet: How Molecular Machines Extract Order from Chaos (17 page)

The biomolecular world is filled with exquisite structure and a mysterious drive for change and motion. In several talks, people presented
motility assays
, a fancy term for attaching protein molecules called myosins to a surface and then seeding fibrous proteins, called actins, on top of the myosins. All these molecules are so tiny that they cannot be easily seen in an optical microscope. To make them visible, the researchers attach little molecular flashlights, fluorophores, to them, which turn the actin filaments into molecular fireflies. Immerse the myosin and actin filaments in a liquid buffer solution, and not much happens, but add an energy storage molecule, called ATP, and all over the surface, actin comes “alive.” Like little nanometer-scale worms, the actin filaments start moving in almost straight paths. Sometimes they hit an invisible obstacle and curve in a new direction. As long as enough ATP is provided, they just keep going and going. What moves them? According to the researchers, it’s the myosin molecules. They act like molecular motors, pushing actin forward with their two molecular “hands” and passing each actin filament from one myosin molecule to the next, like a rock star crowd-surfing.

In other talks, researchers explained how cells change their shapes by polymerizing filaments such as actin or the sturdier microtubules. Filaments are made of small units, which spontaneously form by assembling themselves (polymerization) or by being actively assembled and disassembled by molecular machines. As the filaments grow, they push on the cell surface, creating protrusions. This is how cells move. Yet another set of talks dealt with the intricate structures of cell membranes, the thin shell
that surrounds each cell and separates the inside of the cell from the outside environment. Riddled with specialized pores, the membrane only admits desired molecules into the cell, while undesired molecules are kicked out. Floating on the membrane are the cell’s “TV antennas”: cell receptors waiting for a chemical signal from the outside world. Once a signal arrives, it is transmitted through the membrane, setting up a cascade of activity that may lead to cell motion, cell division, the secretion of a compound, or cell suicide. This is the nanoscale world of our cells.

Life
must
begin at the nanoscale. This is where complexity beyond simple atoms begins to emerge and where energy readily transforms from one form to another. It is here where chance and necessity meet. Below the nanoscale, we find only chaos; above this scale, only rigid necessity.

How do you tell a bunch of sixteen-year-olds how small a nanometer is? I was standing in front of eighty high school juniors from the Macomb County Math and Science Center, trying to explain my research. I needed to get them to imagine the unimaginable. “A nanometer is to the size of a human, as the size of a human is to ten times the distance from the earth to the moon,” I began, but quickly realized that the distance from the Earth to the Moon is not something many of us have experienced firsthand. Little pearls of sweat started forming on my forehead. I tried again: “A nanometer is so small, you would need to slice the width of a human hair one hundred thousand times to reach a nanometer.” Better. But how about translating distance into time? “If I would shrink you to one nanometer in height, you could walk about twenty-five hundred nanometers in one hour. At this speed, it would take you eighty-two
years
(!) to walk the length of a full-sized human, from his toes to the top of his head.” Gasps. They started to realize that a nanometer is not just small—it is so small that the nano-realm is utterly removed from anything we could ever hope to experience. Yet, we can measure this stuff.

Fifty years before my little lecture to future scientists, Richard Feynman, the famous Nobel Prize–winning physicist, gave a groundbreaking lecture to fellow physicists at the 1959 American Physical Society meeting. In typical Feynman fashion, the lecture was simply titled “There’s Plenty
of Room at the Bottom.” The “bottom” was the microscopic scale, from micrometers (one thousand nanometers) down to atoms at just a few tenths of a nanometer in diameter. Feynman’s point was that no law of physics should keep us from creating machines that are just a few nanometers large. It’s simply a question of engineering.

It took a while for Feynman’s vision to become reality, but by the late 1980s, nanotechnology was starting to take off. With the invention of tools to image objects only a few nanometers in size and to measure and manipulate them in various ways, it was now possible to compress data to nanoscale bumps or to build ever-more-complex nanostructures. These advances led to a kind of frenzy of wild predictions in the 1990s and into the 2000s, some overhyped (nanotechnology as the savior for all our energy, medical, and environmental problems) and some doomsday (gray goo of nanorobots eating everything in sight—as in the remake of
The Day the Earth Stood Still
or in Michael Crichton’s book
Prey
).

At least in the media, the nanotechnology craze has died down a bit. The early promises of nanorobots (or nanobots) cleaning plaque out of our trans-fat-challenged arteries have not materialized as fast as expected. The dangers of nanotechnology are there (small nanoscale fibers can possibly cause cancer—think asbestos), but the gray-goo idea seems highly overdrawn. The media have moved on. But in science, nanotechnology and nanoscience are alive and well. Scores of physicists, engineers, chemists, and medical researchers are engaged in nanotechnology research, from nanobatteries to nanomedicine.

Personally, I prefer to speak of nanoscience rather than nanotechnology. Nanotechnology is the next step, after the science has been worked out. What is nanoscience? In short, it is the production, measurement, and understanding of systems where at least one spatial dimension is in the nanometer range. Sometimes, this broad definition has led to trouble, as many old areas of research, such as thin-film technology and some branches of chemistry, suddenly became nanotechnology research, only because they dealt with things smaller than one micrometer. Thus there is a joke about nanotechnology—that it is simply a ruse to get money out of funding agencies. While there was some truth to this charge—at least in the early days—there is something genuinely special about the nano-scale:
Systems, once shrunk down to this “magic” scale, exhibit new and rather unexpected properties.

Feynman’s talk at the 1959 American Physical Society meeting is often credited as having jump-started the nanoscience revolution. The truth, however, is a bit more complicated. When he gave his famous talk, the assembled listeners did not take the topic very seriously. One attendee of the meeting recalls: “The general reaction was amusement. Most of the audience thought he was trying to be funny . . . It simply took everybody completely by surprise
.
”
^*
Feynman’s talk was rediscovered twenty-five years later, when many of his predictions had come to pass. By then, technology had caught up with many of Feynman’s visionary ideas, and they were finally taken seriously.

Feynman took his inspiration from living systems, as have many recent nanotechnology visionaries. He was taken by the way information was written “on a very small scale” in biological cells, and how cells used the information to “manufacture substances,” “walk around,” and “do all kinds of marvelous things.”
^**
Indeed, if today’s nanotechnologists are dreaming of building nanosize machines, they have to accept that nature beat them to the punch by a mere three billion years! Living cells are teeming with molecules that perform amazing feats at a nanoscale with almost uncanny precision.

Feynman envisioned that nanoscale miniaturization would allow us to store whole books on the head of a pin, build tiny motors, move single atoms around, or build powerful pocket-size computers. All of these things have come to pass. Some of his other predictions are still not feasible, such as the creation of a nanosize surgeon, an idea we now know as the nanobot. A nanobot would be a tiny device that could be swallowed like a pill or injected into the bloodstream. The device would perform nanosurgery, such as cleaning plaque from arteries or performing search-and-destroy missions on cancer cells. However, in a field called targeted drug delivery, or nanomedicine, researchers have already made remarkable progress
in creating nanostructures which will specifically seek targeted cells (for example, cancer cells) and then deliver their payload (deadly drugs to a cancer cell, or a piece of DNA to repair gene damage) only to the targeted cells. Another one of Feynman’s predictions, which he took from a science fiction story by Robert Heinlein, was the possibility of building a machine that could construct a smaller version of itself. The smaller version, in turn, could build an even smaller version. Like a set of Russian nesting dolls, the machines would build smaller and smaller versions of themselves, all the way down to the last, nanometer-size machine.

Similar ideas of tiny machines made of molecular gears propelled an MIT engineer, K. Eric Drexler (b. 1955), to write a now-famous book about the possibility of molecular machines. When he read Feynman’s talk in the late 1970s, Drexler had already thought about the possibility of making machines out of molecules, and reading Feynman gave him an additional impetus. In 1986, he published the founding work of modern nanotechnology:
Engines of Creation: The Coming Era of Nanotechnology
. Much of Drexler’s ideas have so far remained science fiction, although there has been substantial progress in some areas. For example, moving single atoms and molecules around one by one and making structures such as circles or triangles made of atoms on a surface is, if not routine, certainly an achievable feat with the right tools.

The right tools were being invented about the same time Drexler wrote his books. The most iconic of these tools, scanning probe microscopes, had a great impact on the burgeoning science of the nanoscale and an equally great impact on my own life.

When you defend your Ph.D. at the University of Oxford, you’d better know your stuff. Examiners are brought in from other universities, preferably from outside the country. They don’t know you, but are there to ensure you’re no slacker. When my friend Steve got his Ph.D. at Oxford from his work with atomic force microscopes (AFMs), his examiners were two of the best-known AFM experts in the world: Christoph Gerber, who together with Nobel Prize–winner Gerd Binnig, had invented and built the world’s first AFM in 1986; and Ernst Mayr, who
runs one of the largest and most successful AFM groups in the world. Gerber, who works for IBM, is a technical genius. When he visited Oxford in 2000 to be an examiner for Steve’s Ph.D. defense, he told us about a new AFM spinoff: an artificial nose. This nose works by coating tiny cantilevers (micrometer-long beams of silicon) with different substances that absorb airborne chemicals. When the chemicals are absorbed, the substance on the cantilever expands, and the cantilever bends. Using an array of differently coated cantilevers, each sensitive to different types of chemicals, this mechanical nose can be trained to distinguish many different smells. Gerber, a connoisseur of Scottish whiskeys, was excited to find that his mechanical nose had no problem distinguishing a Craigellachie from a Laphroaig, but he was even more surprised when the nose told him that one of his whiskeys had a hint of cherry. He called up the distillery in Scotland, and, indeed, the whiskey had been aged in cherry wood casks.

The AFM is the most common member of a group of instruments called scanning probe microscopes (SPMs). SPMs have revolutionized the measurement and manipulation of matter at the nanoscale more than any other instrument invented since Feynman’s famous talk. The first SPM was the scanning tunneling microscope (STM), invented in 1982 by Gerd Binnig, Christoph Gerber, and Heinrich Rohrer at the IBM laboratory in Zurich, Switzerland. The capability of this new instrument to image single atoms and measure their electronic properties was so astounding that Binnig and Rohrer received the 1986 Nobel Prize for their invention.

The working principle behind SPMs is surprisingly simple. Instead of detecting light from an object, as we would do in conventional microscopy, SPMs “feel” the surface by means of a sharp probe. The way the SPM feels the surface depends on the nature of the probe: In a STM, the microscope feels a “tunneling current” between the probe (a sharp metallic needle) and a conducting surface. Tunneling, a purely quantum-mechanical effect, is the ability of an electron to traverse an energy barrier it should not be able to cross, according to classical physics. In STM, this energy barrier is posed by the gap between the probe and the surface it is imaging. The tunneling current measured by STM depends on the width of the barrier (the distance between the probe and the surface) and the amount of electrons in the sample. Measuring the tunneling current across a sample
surface provides a map of the changing heights on the surface, or changing electron density, or both. Tunneling is so sensitive to tunnel barrier width that each time the probe is moved away from the surface by only a tenth of a nanometer, the tunnel current decreases by a factor of ten! This extreme sensitivity allows the STM to obtain images of single atoms.

The images obtained with an STM are a convolution of changing heights on a surface and the changing electron densities (which vary around atoms). However, that’s not all. Forces between atoms on the tip and surface also play an important role. This was becoming clear soon after the invention of STM, when eager researchers around the world built their own STMs to look at a plethora of different surfaces. On some surfaces, the images obtained did not square with theoretical predictions taking only tunneling barrier widths and electron densities into account. One group of researchers, for example, noted that on some surfaces, the forces were so high that the distance calibration of the instrument was thrown off. This problem was addressed with the invention of a second, and now the most popular, scanning probe microscope, the AFM.