biomolecules or molecules in a structured environment.8 The technique lays the groundwork for achieving the control of an individual molecule’s motion. Ultimately, this work may lead to such practical applications as miniaturized sensors.

The four assert that studying single molecules is important because molecular individuality plays an important role even when molecular structure is complex. An intricate internal structure such as that found in a biomolecule, for example, results in a complex energy landscape. Alternatively, the molecule may be influenced by environmental factors that substantially change its behavior. Thus, the ability to distinguish different molecules under differing conditions and structures becomes crucial for understanding the system as a whole.

Biomolecules in living cells are one such example, the quartet explain. Even simple inorganic molecules on structured surfaces or in disordered systems, such as viscous liquids or glasses, provide situations in which molecular individuality matters. In all of these cases, the ability to study an individual molecule over time can give new insights unavailable by straightforward experiments on macroscopic populations of molecules. The new questions that single-molecule experiments pose move chemistry and physics into a realm more familiar to astronomers, who have direct observational knowledge of a single complex object such as the universe, and who must infer underlying rules and patterns. A single molecule under active control may well resemble the elegant engineered machinery rather than the “wild” molecules created by and found commonly in the natural world.

Tiny Building Blocks

As Wooley et al. point out, over the past decade, polymer chemistry has attained the sophistication necessary to produce macromolecules with accurate control of structure, composition, and properties over several length scales, from typical small-molecule, angstrom-scale resolution to nanometer dimensions and beyond.9 Most recently, methods that allow for the preparation of polymeric materials with elaborate structures and functions—“bioinspired” materials—have been modeled from biological systems.

The four explain that, in biological systems, complexity is constructed by the ordering of polymer components (that is, polymers of amino acids, saccharides, and nucleic acids) through a combination of covalent bonds and weak interactions (such as hydrophobic, hydrogen bonding, and electrostatic interactions), with the process being controlled by the specific sequence compositions. An


Frontiers of Science/1998. Chunli Bai, Chen Wang, X. Sunney Xie, and Peter G. Wolynes, at <>.


Frontiers of Science/1999. Karen L. Wooley, Jeffrey S. Moore, Chi Wu, and Yulian Yang, at <>.

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