Nature Methods

Research in the January issue of Nature Methods shows a newly-designed ‘caging’ molecule, which allows scientists to precisely time the release of specific biological molecules into living cells via a sensitive activation process that helps keep cells alive and well.

Just like one might build a wire cage to trap birds or mice, scientists can also assemble chemical cages for trapping equally wily prey—the biologically active small molecules that drive a variety of cellular processes. These caging compounds are often photoreactive, with the caged molecule remaining inactive until bombarded with light of an appropriate wavelength. The light disrupts the cage and releases the molecule, restoring its functionality and enabling scientists to subsequently monitor the cellular responses that occur as a result of release.

This approach is useful, but it has proven difficult designing caging compounds that react quickly and efficiently. Sensitivity is also an important issue, for many of these reagents require the use of light so intense that it can damage or even kill the cells being studied.

Now, Graham Ellis-Davies and his colleagues describe their new contribution to the field, NDBF. In initial studies, they show that their compound reacts to light with an efficiency that surpasses existing compounds by orders of magnitude. Best of all, uncaging can be performed by two-photon photolysis—a low energy alternative that is far safer for cells, and therefore a better choice for ensuring the quality of experimental data. In this article, NDBF was used to cage calcium within cardiac muscle cells, where sudden calcium release results in contraction. However, the authors believe that the simple chemistry behind NDBF caging should make it a general purpose tool for use with a variety of other small molecule targets.

CONTACT
Graham C.R. Ellis-Davies (Drexel University College of Medicine, Philadelphia, PA, USA)
Tel: +1 215-762-8794; Email: ged@drexel.edu

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