Energy in motion: how the nanomachines of life harvest randomness to do the cells' work

Science News,  Feb 23, 2008  by Davide Castelvecchi

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Occasionally, scientists stumble upon what seems to be a free lunch. But they re not concerned about possibly violating the laws of economics. It would be much more shocking to break the laws of physics.

To physicists, the no-free-lunch rule is precious. One form of it is the first law of thermodynamics, which says that energy cannot be created from nothing. The second law of thermodynamics goes even further, declaring not only that lunches are never free but also that they come at some minimum price.

Nonetheless, some natural phenomena seem, at first glance, to violate the spirit, if not the letter, of those laws. Take living cells. In recent years, scientists have found that some molecular machines--proteins that perform crucial tasks of life, from shuttling molecules through membranes to reading information off of DNA--seem to move spontaneously. These machines are likely powered by the random motion of water molecules in their environment, the "thermal noise" that thermodynamics insists is not available for doing work.

While some researchers debate how such machines work without breaking physical laws, other scientists have begun to exploit similar phenomena to create artificial molecular motors--nanomachines that imitate nature by putting randomness to work. "The idea is, let's take advantage of thermal noise, rather than fight against it," says Dean Astumian, a theoretical chemist at the University of Maine in Orono.

Researchers have just begun to build artificial nanomachines that perform simple tasks, such as moving molecules, by steering random motion in one direction rather than another. In the Feb. 13 Journal of the American Chemical Society, a team led by David Leigh, a chemist at the University of Edinburgh in Scotland, describes the first molecule designed to use chemical energy to open or close a gate and allow one of its parts to randomly cross the gate in one direction, but not the other.

It's very much like the task assigned to a hypothetical "demon" by the 19th-eentury Scottish physicist James Clerk Maxwell. His thought experiment was an early attempt to show how the second law defines group behavior and thus applies only to large numbers of particles.

MAXWELL'S ANGEL The second law requires that in any given activity, some of the expended energy will end up as waste heat.

For example, even an efficient power plant can lose half or more of its fuel's energy to waste heat. This waste heat cannot be recovered without expending more energy--and producing more waste heat--in the attempt.

Ultimately, waste heat manifests as random molecular motion, like the incessant hailstorm of water molecules buffeting proteins in a cell's watery guts.

"It's sort of like you're riding a bicycle and there's a Richter-12 earthquake going on all the time," says George Oster, a molecular biology theorist at the University of California, Berkeley.

It's hard to see how the molecular movements (called Brownian motion) produced by such violence could accomplish anything useful. Every second, a typical molecular motor will exchange millions of times as much energy with the environment through these random collisions as it will in the performance of its actual task, Astumian explains. But beginning in the early 1990s, scientists began to suspect that certain protein motors can perform their tasks not despite Brownian motion, but thanks to it.

One example is RNA polymerase (RNAP), an enzyme responsible for reading genetic information from DNA. RNAP latches on to a DNA double strand at the beginning of a gene, cleaves the two strands apart, and clamps around one of them. It then moves along DNA's bases--the A's, C's, G's, and T's that constitute the genetic code's alphabet--and assembles a corresponding molecular chain of RNA. The RNA molecule then acts as a template for producing proteins.

RNAP, however, does not always move forward. Brownian motion can push it either way. "It's like a zipper--it slides back and forth," says Evgeny Nudler, a biochemist at New York University.

Roger Kornberg, a structural biologist at Stanford University, and his collaborators first decoded the structure of RNAP in 2001, earning him the 2006 Nobel Prize in Chemistry. In the same award-winning papers, the team suggested that RNAP maybe able to select the Brownian fluctuations that propel it forward and discard those that would set it back. That sounds suspiciously like a free lunch, but in fact, the laws of physics do not prevent it.

RNAP's secret lies in the fact that the second law is statistical in nature. At the scales of molecules, random fluctuations can temporarily create small amounts of seemingly "free" energy. Cells can take energy out of Brownian motion by selecting the favorable fluctuations and rejecting the others--very much in the spirit of Maxwell's demon.

Maxwell asked whether the random differences among the energies of particles could somehow be harnessed. He imagined a box filled with a gas and divided into two parts by a wall that didn't conduct heat. The wall had a tiny door, and standing by it, "a being whose faculties are so sharpened that he can follow every molecule in its course," Maxwell wrote in Theory of Heat (1871). This "demon" could open or close the door whenever a gas molecule approached, in such a way as to let the faster molecules cross in one direction only, and the slower ones in the opposite direction. After a while, the faster molecules would make one side of the box hotter than the other. Heat would flow in the "wrong" direction.