Jan 282013

In 2005, the 125th anniversary of Science magazine, that journal produced a list of the 125 questions on what we don’t know. Among the Top twenty-five was: How Far Can We Push Chemical Self-Assembly? Robert Service wrote that

… chemists thrive on finding creative new ways to assemble molecules. For the last 100 years, they have done that mostly by making and breaking the strong covalent bonds that form when atoms share electrons. Using that trick, they have learned to combine as many as 1000 atoms into essentially any molecular configuration they please.


… this level of complexity pales in comparison to what nature flaunts all around us. Everything from cells to cedar trees is knit together using a myriad of weaker links between small molecules. These weak interactions, such as hydrogen bonds, van der Waals forces, and p-p interactions, govern the assembly of everything from DNA in its famous double helix to the bonding of H2O molecules in liquid water. More than just riding herd on molecules, such subtle forces make it possible for structures to assemble themselves into an ever more complex hierarchy. Lipids coalesce to form cell membranes. Cells organize to form tissues. Tissues combine to create organisms. Today, chemists can’t approach the complexity of what nature makes look routine.

He concluded by asking, “Will they ever learn to make complex structures that self-assemble?”

Taking “self-assembly” as a compound word, it sounds like it applies to structures that assemble themselves. But many scientists assume more than that: the phrase “shake and bake” applies to the process of adding the correct ingredients to a pot containing the correct media, along with the correct catalysts, heating it and cooling it by the correct sequence of temperatures over the correct time span, et voila! A nano-scale Swiss watch.

Shake and bake is what the alchemists did, and while it is quite powerful – that’s how we got those structures of up to a thousand atoms joined by covalent bonds – we shouldn’t expect to build a watch this way. In fact, an economist (!) addressed the watchmaking problem in a seminal paper on The Architecture of Complexity, and proposed an alternative process he observed in social systems – and others have observed in nature. Herbert Simon imagines two watchmakers. One assembles a watch from its components, one watch at a time from scratch. The other assembles basic components into modules, one module at a time, making umpteen modules of type A, umpteen of type B, and so on, then modules into super-modules, umpteen of type I, umpteen of type II, and so on, and then puts together the super-modules into umpteen watches. This hierarchical construction reduces the number of errors and increases efficiency. It is also the way Mother Nature does things in biology.

Contrary to the image of “protoplasm” entertained by biologists of a century ago, biologist now envision a cell as a highly organized structure, with partitions, communication links, supporting superstructure, all serviced by armies of protein molecules, each a specialist in a particular task. These protein molecules do not wander around in a crowd; they move around in compartments, corridors, and other spaces, encountering other entities that are supposed to be there. The cedar trees that Service describes as structures currently beyond our technology were the result of constrained if not managed assembly.

Since biological systems are the most familiar ones employing managed assembly, we should expect managed assembly in the literature to be heavily biological at first. For example, Bartosz Lewandowski et al report in Science that Sequence-Specific Peptide Synthesis by an Artificial Small-Molecule Machine. Here, they “report on the design, synthesis, and operation of an artificial small-molecule machine that travels along a molecular strand, picking up amino acids that block its path, to synthesize a peptide in a sequence.”

The trick will be to organize many of these little tasks within a controlled space to get … a factory. And factories will be able to build things way beyond anything we’ve made thus far.