University of Colorado, Boulder

A biologist looks to 'click chemistry' for better three-dimensional tissue models.

A hot topic in organic chemistry is the development of ways to neatly home in on a particular chemical group and cause a reaction to proceed extremely efficiently under mild conditions. Such highly optimized reactions have been grouped under the term 'click chemistry'. A commonly cited example involves functional groups called azides and alkynes, which react to form triazoles with the aid of a copper catalyst.

Click chemistry has all sorts of uses, although few are in biology because the technique relies on toxic metal catalysts. However, Carolyn Bertozzi and her colleagues at the University of California, Berkeley, and the nearby Lawrence Berkeley National Laboratory recently demonstrated copper-free click chemistry in a living system (J. M. Baskin et al. Proc. Natl Acad. Sci. USA 104, 16793–16797; 2007). These authors selectively — and rapidly — labelled cell-surface polysaccharides with with triazole bound to a fluorescent probe. The technique allows real-time imaging of cell surface molecules that are otherwise impossible to achieve.

This research throws open the door for a host of new applications for click chemistry. As a tissue engineer, I am particularly excited about exploiting it to make better gels for three-dimensional cell culture.

Physiological processes are routinely guided by interactions between cells and their tissue environment. Thus, a major hurdle in tissue regeneration is knowing which biochemical signals must be recapitulated in cell culture, and how to present them at the appropriate time and place. Copper-free click chemistry could allow scientists to synthesize materials that deliver these signals at times that are governed by the physiological conditions in which the material resides. Next on my wish list is the ability to control the spatial organization of these reactions.