Breakthrough in artificial signalling

Derrick Roberts co-first author on paper on the use of self-assembled molecular cages to transmit molecular signals.

A reaction cascade is like the Olympic torch relay, where each runner represents a single chemical reaction, and the torch represents a chemical signal.

Derrick Roberts and Ben Pilgrim

Scientists have developed a way to transmit molecular signals using artificial self-assembled molecular cages – which could eventually lead to the construction of complex chemical sensors and reactors with broad applications for industry and medicine.

The research, 'Signal transduction in a covalent post-assembly modification cascade', was published in Nature Chemistry last week. Gates Cambridge Scholar Dr Derrick Roberts [2012] and Dr Ben Pilgrim from the Department of Chemistry at the University of Cambridge are co-first authors.

It investigates how self-assembled molecular cages can be used in artificial signal transduction, which is inspired by molecular signalling from a cell’s exterior to its interior. It focuses on reaction cascades, which are sequences of two or more chemical reactions connected so that the output of one reaction serves as the input of another. This is one of the main ways cells send and receive signals.

The co-authors write: “A reaction cascade is like the Olympic torch relay, where each runner represents a single chemical reaction, and the torch represents a chemical signal. The relay begins with the torch (signal) in the hands of the first runner (the first reaction), with each subsequent runner waiting for the torch before starting their leg of the relay. The torch travels great distances as it is passed from runner to runner until it reaches the Olympic stadium. Similarly, the sequential reactions in a cascade can carry a microscopic chemical signal across macroscopic distances. Cells make use of this relay effect to transmit biochemical signals around the body.”

Inspired by the role of reaction cascades in biological signalling, the researchers designed a non-biological signal transduction system that could model key features of its biological counterparts. The cascade system was comprised of two self-assembled molecular cages: a cube, which is empty, and a tetrahedron, which carries a payload (a negatively charged ion) within its central cavity. Initially, both cages are dissolved in a polar solvent called acetonitrile and they are not easily separated. The addition of a signalling molecule triggers the reaction cascade, which results in the addition of long chains of carbon and hydrogen atoms (which are very greasy or ‘lipophilic’, meaning they tend to dissolve in fats or lipids) to the tetrahedron. As a result, the tetrahedron becomes less soluble in acetonitrile than the cube, allowing it and its payload to be extracted into a more oily (non-polar) solvent.

The researchers say their study offers the first proof-of-concept for achieving the transmission of molecular signals from a cell's exterior to its interior using a reaction cascade that features self-assembled cage molecules. They add that their ability to selectively separate two initially inseparable cage molecules may prove important for developing new separation techniques and more sophisticated catalyst systems.

Derrick, who was based at Trinity College, says: “One of the most promising applications for molecular cages to use them as "nanocontainers" – tiny little spaces that can trap specific molecules or that can host chemical reactions. My vision for our research is to use reaction cascades to control the behaviour of these nanocontainers, such as instructing them to capture or release a guest molecule, and to direct their phase behaviour (i.e., whether they will dissolve in a water-like or oil-like phase).

“This level of control could allow scientists to build sophisticated chemical reactors that would revolutionise how the chemical industry makes important compounds, from medicines to agrochemicals. It could also allow scientists to build complex chemical sensors to detect environmental pollutants or tiny levels of chemicals in the bloodstream for the early diagnosis of diseases like cancer.”

Picture credit of Seoul Olympic toruch: Wikimedia.