The term "molecular machine" first entered the vocabulary of science in the late 1980's. Today a search on Google™ for the term, or its derivatives (protein machines and molecular motors) yields over 60,000 hits. In the biosciences, the term refers to a complex biomacromolecule (or a localized assembly of biomacromolecules) that consumes energy in order to perform a specific action. According to the Foresight Institute, a non-profit devoted to educating society about nanotechnology; a molecular machine is, "A mechanical device that performs a useful function using components of nanometer scale and defined structure."
The Foresight Institute goes on to say that this definition, "includes both artificial nanomachines and naturally occurring devices found in biological systems," which leaves open the possibility that man made machines could function in the same way. However, there is a huge disparity between the specificity of natural machines and their man-made counterparts. The measure of a molecular machine’s specific action is nicely summarized by Thomas D. Schneider, “the precise measure of the specific action … is the number of distinct states which the machine can choose between.”
Even a simple biological molecular machine will chose between many states. For example the DNA cutting protein, EcoR1, cuts at a specific 6 base sequence, thus selecting 1 position out of 4^6 = 4096 possible positions, or gaining log2 4096 = 12 bits of information per operation in a one dimensional system comprised only of EcoR1 and random DNA (the actual information gained in a three dimensional system filled with competing binding sites is arguably much higher).
Examples of man-made molecular machines (nanomachines), such as the spinning nanotube of Alex Zettl at UC Berkeley, are crude in comparison to naturally occurring machines. Generally, these nanomachines have components that are much larger than the nanometer scale, and the action they perform only discriminates between two states, such as clockwise or counterclockwise spinning. Additionally, many nanomachines use DNA and other biomacromolecules as a starting point, and thus are hybrids of natural and artificial machines.
The growing interest in biological molecular machines over the past two decades can be traced to enthusiastic articles in leading scientific journals, such as the review written by Bruce Alberts, the National Academy of Science president, in the journal Cell. He and others helped explain (to otherwise design-language adverse biologist) the reason for using very design friendly terms such as "molecular machine", or "protein machine". In answer to the question, "Why do we call the large protein assemblies that underlie cell function protein machines?" (emphasis in original). Alberts responds, "Precisely because, like machines invented by humans to deal efficiently with the macroscopic world, these protein assemblies contain highly coordinated moving parts"
Today, the use of this analogy to human-designed machines is pervasive. With this analogy as our guide, we can arrive at a good understanding of molecular machines--their structure, composition, and mechanical, chemical or electrical functions. In addition, three difference between molecular machines and man-made machines are important to keep in mind.
First, molecular machines are made not from metal and plastic, but from biomacromolecules (protein, DNA, RNA, and carbohydrates). All of these macromolecules exist as chains (branched chains in the case of carbohydrates), in which each “link” can be one of several possible subunits, which are distinct for that type of chain. Most often, molecular machines are made of protein, which uses amino acids as its distinctive subunits, of which there are typically 20 possibilities. The precise arrangement of the 20 possible amino acids allows the protein to collapse upon itself into a precise three-dimensional shape. This shape confers the function to the molecular machine. For example, EcoR1 has a clamp-like three-dimensional shape that binds and recognizes six specific subunits of DNA. If the one-dimensional chain of subunits is altered, the three-dimensional shape will also be changed and the function will be affected. This is the basis of the adage, "Beneficial mutations are few and far between." Mutations correspond to a change in the sequence of a protein chain, and a benefit would be an improved function. Since most molecular machines are already functionally optimized, virtually all perturbations to their sequence adversely affect their function.
Second, in order to properly perform their tasks, each molecular machine requires a particular type of fuel molecule, a strictly regulated environment and, most often, other complementary machines. The first two requirements can be met in vitro (e.g. in a test tube) by careful experimental design. Indeed, our recent discoveries in molecular biology have been due to our ability to utilize natural molecular machines to copy and manipulate DNA and RNA, synthesize, purify and modify protein, and assay and image natural systems. For example, it has become possible, using DNA modifying molecular machines, to insert the gene for a jellyfish's light-converting (fluorescent) machine into various organisms, and then observe under a fluorescence microscope the shuttling of this machine from one part of the organism to another. However, the fact that molecular machines require fuel and an environment regulated by other machines (or experimenters), put constraints on the likelihood that these complex devices would originate by chance.
Third, molecular machines operate in a physical environment that is much different from what we experience day-to-day. Most noticeably, molecular machines are constantly bombarded by water molecules and other particles. This would make the machines look like they were "shivering and shaking" if we could observe them directly. Interestingly, these machines actually use their shaking to help them overcome hurdles to their progress, much like a few whacks with a hammer can help a rusty motor start rotating. Another difference is that molecular machines experience no inertia. They are so tiny that their momentum is instantly stopped by the frictional force of the water that surrounds them. Even if a molecular machine were traveling as fast as a space shuttle entering earth's atmosphere (scaled for its size) it would stop—the moment it turned off the force used to propel itself forward—in less than an inch (or a trillionth of an inch, when scaled to the right dimensions). This lack of inertia means that molecular machines must find ways of moving through their surroundings other than the more macroscopic "push and glide" approach.
Ever buffeted by particles, unable to maintain motion without constantly burning fuel, the job of a molecular machine is by no means easy. And with tight dependence on subunit sequence, a regulated environment and additional machines, it is not surprising that every attempt to hypothesize the abiogenesis of an early molecular-machine has been met with utter failure. Molecular machines continue to defy explanation by chance alone.
Web Resources On Molecular Machines
Gallery of Molecular Machines
Theory of Molecular Machines
Molecular Machines and Motors
Book Resources On Molecular Machines
Molecular Biology of the Cell by Bruce Alberts
Molecular Machines & Motors by Jean-Pierre Sauvage
Molecular Devices and Machines : A Journey into the Nanoworld by Vincenzo Balzani
Editor(s): Jed Macosko