Life's Ratchet: How Molecular Machines Extract Order from Chaos (22 page)

FIGURE 4.5.
Measurement of the stiffness and damping of molecule-thick water layers, using an atomic force microscope (AFM). Each peak in the stiffness (filled circles) corresponds to a thickness of water between the AFM tip and a flat surface, which contains an integer (1, 2, 3, . . .) number of water molecules. The fact that the stiffness peaks and the damping peaks (open circles) don’t line up means that the few-molecules-thick water layer responded like a solid to being squeezed by the AFM tip.

The same thing can happen for bulk liquids (i.e., liquids that are not confined to nanometer spaces), but only at very fast speeds. Our finding was that at the nanoscale, these dramatic changes happened at very, very slow speeds. But how is that possible? Molecules in a liquid move at incredible speeds, much faster than our AFM tip. They should have plenty of time to accommodate the approaching tip, and the liquid should remain liquid. The answer is—you guessed it—cooperativity. Once water is squeezed to just a few molecular layers between the surface and the tip, it becomes difficult for the water molecules to move out of the way of the approaching tip. Due to the confinement, the molecules don’t have the freedom of motion they enjoyed in the bulk. When confined to the nanoscale, many molecules have to move in concert to create a hole into which the tip will move—water molecules have to cooperate to move out of the way. What is truly remarkable about these results is that it takes water molecules extremely long, of the order of seconds, until they
randomly
happen to move in a coordinated manner to create a hole. That is a million billion times longer than the average time between water molecule collisions. A crude calculation indicates that thirty to forty molecules—not very many—would have to be involved in the collaborative motion to create such a long time scale. Cooperativity can create not only sharp transitions, but also large changes in time scales, making even molecular processes take seconds or even minutes.

Amphiphilic molecules, such as lipids and detergents, suddenly form micelles once they reach a critical concentration. This results in a sharp change in osmotic pressure. In our confined-water experiments, we saw a rapid switching from liquid-like to solid-like behavior in response to a small increase in squeeze rate. The occurrence of rapid changes at critical values for certain control parameters (concentration for micelles, speed for confined water) is a signature of cooperative behavior.

Cooperative behavior is not restricted to molecular biology. It is a ubiquitous, but underappreciated facet of our world. For example, some economists have argued that the financial crisis of 2008 and others before it, including the Great Depression of the 1930s, were the result of a cooperative failure of banking. This is how it goes: There is always a low rate of bank failures. As long as that rate is low, the overall financial system is relatively unaffected. But if banks fail at a rate exceeding a certain critical threshold, the interconnectedness (cooperativity) of banks pulls the whole market into the abyss. Thus, what looks like another, albeit somewhat larger, fluctuation in the financial market suddenly leads to rapid, profound change. This is cooperativity at work.

Cooperativity leads to
switching
. Yesterday everything was fine; today the economy has crashed. A second ago, lipid molecules were happily floating around, and then, suddenly, they form micelles, and osmotic pressure drops precipitously. Water acts like a liquid, but squeezed above a slow critical rate, it suddenly bounces like rubber. A DNA double helix was fine a second ago, but suddenly it catastrophically unzips when it is heated. The San Andreas fault was quiet an hour ago, and now all hell breaks loose. We should not underestimate cooperativity!

Despite some of the negative examples of its effects, cooperativity is crucial for the function of living cells. Changes in a molecule’s shape are driven by cooperativity of many bonds, and the shape change, often sudden and dramatic, can be driven by a relatively small external change. This behavior allows for the creation of
molecular switches
, molecules that can effect large changes in response to small causes, such as the binding of a small molecule. This in turn allows the creation of
molecular circuits
, which
control the activity in a cell. In electronics, a transistor is an element that allows a small change in a voltage to control a large current. Transistors are electronic switches, and they are the root of modern electronics, from radios to computers. Similarly, molecular switches in cells serve as control units to make cells work. They work on the principle of cooperativity, which in turn is made possible by the use of many small bonds, many of them of entropic origin.

Thermal motion, entropic forces, and cooperativity—some of the strange properties of nanoscale systems—are important for our understanding of life at the molecular scale. Another, truly astonishing property of the nanoscale is
the
key to understanding how the coordinated activity of cells is generated. This property relates to how energy is transformed from one form to another. One of the most astonishing features of life is that living beings can take energy from food and turn it into directed motion. Past generations attributed this magical feat to life forces. However, the continued search for physical explanations has brought scientists to the molecular scale. Proteins, DNA, RNA, and other large molecules inside cells seem to be the fundamental functional units that make the cells work. Some of these molecules must be able to convert energy from one form to another; they must be acting like
molecular machines
.

Machines are energy-conversion devices—a car engine, for example, converts chemical energy into kinetic energy. However, a car engine sitting in a pool of gasoline with no connections would not jump to life. Yet, the molecular machines in our cells do just that: Pluck a molecular machine, such as myosin, out of a cell, give it some chemical fuel (called ATP in cells), and it will “come to life.” Molecular machines are autonomous machines. Why can molecular machines work autonomously, while our familiar, macroscopic machines cannot?

It turns out there is something very special about the nanoscale when it comes to converting different forms of energy into each other. Intriguingly,
only
at the nanoscale are many types of energy, from elastic to mechanical to electrostatic to chemical to thermal, roughly of the same
magnitude (
Figure 4.6
). This creates the exciting possibility that the molecules in our bodies can
spontaneously
convert different types of energy into one another. Molecules and small, nanoscale particles can have substantial fluctuations in energy as they take energy from the molecular storm (thermal energy), use it to convert, for example, chemical energy to electrical energy, and then release the energy again into the surrounding chaos. By contrast, smaller structures, such as atoms or nuclei, have binding energies that are too large to allow thermal energy fluctuations, unless the temperature (along with thermal energy) is extremely high (thousands or millions of degrees). At such high temperatures, molecules are unstable and the formation of complex structures needed for life is impossible. On the other hand, at scales much larger than a nanometer, mechanical and electrical energies are too high to be subject to thermal fluctuations. At this scale, everything becomes deterministic, and objects do not spontaneously change shape or assemble themselves—which are attributes needed for life.

FIGURE 4.6.
Electrostatic energy, chemical bond energies, and elastic energies all converge at the nanoscale (10
⁻⁹
meters), where they meet thermal energy (the molecular storm) at room (or body) temperature. This confluence of energy scales at the nanoscale explains self-assembly and the possibility of molecular energy conversion devices and machines. Reprinted with permission from Rob Philips and Stephen R. Quake, “The Biological Frontier of Physics,”
Physics Today
59 (May 2006): 38–43. © 2006, American Institute of Physics.

Thus, the nanoscale is truly special. Only at the nanoscale is the thermal energy of the right magnitude to allow the formation of complex molecular structures and assist the spontaneous transformation of different energy forms (mechanical, electrical, chemical) into one another. Moreover, the conjunction of energy scales allows for the self-assembly, adaptability, and spontaneous motion needed to make a living being. The nanoscale is the only scale at which machines can work completely autonomously. To jump into action, nanoscale machines just need a little push. And this push is provided by thermal energy of the molecular storm.

But doesn’t the molecular storm always lead to chaos, as suggested in the discussion of the second law of thermodynamics in
Chapter 3
? The answer would be yes if the molecular machines of living cells were just any old molecules—but they are not. They are clever little machines that can sift order out of chaos. How? Let’s find out.

Richard Feynman quotation by permission of California Institute of Technology,
Engineering and Science Magazine
. K. Eric Drexler quote courtesy of K. Eric Drexler.

*
Christopher Toumey, “Reading Feynman into Nanotechnology: A Text for a New Science,”
Techné
12, no. 3 (fall 2008): 133–168. Tourney ascribes the quote to Paul Shlichta, then of the Jet Propulsion Laboratory, California Institute of Technology, Pasadena.

**
Richard Feynman, “There’s Plenty of Room at the Bottom,”
Caltech Engineering and Science
23 (February 1960): 22–36, available at
www.zyvex.com/nanotech/feynman.html
.

Now let us suppose that . . . a vessel is divided into two portions, A and B, by a division in which there is a small hole, and that a being, who can see the individual molecules, opens and closes this hole, so as to allow only the swifter molecules to pass from A to B, and only the slower ones to pass from B to A. He will thus, without expenditure of work, raise the temperature of B and lower that of A, in contradiction to the second law of thermodynamics.

—J
AMES
C
LERK
M
AXWELL
,
T
HE
T
HEORY OF
H
EAT

The Moving Finger writes; and, having writ,
Moves on: nor all thy Piety nor Wit
Shall lure it back to cancel half a Line,
Nor all thy Tears wash out a Word of it.

—O
MAR
K
AYYAM
, 1048–1131