Active Substance Optically Manipulates Component of Cytoskeleton

An international research team from Jena, Munich, and New York has used photopharmacology — the use of light to switch the effect of drugs on and off — to control actin, a component of cells that was previously considered inaccessible.

“Up to now, there were no drugs available that targeted actin, because the protein is found everywhere in the body,” professor Hans-Dieter Arndt of Friedrich Schiller University said. “Such a substance would therefore have little to no targeted effect. However, our new compounds only exert activity on actin in areas where cells are exposed to the appropriate light.”

The researchers synthesized a variant of a natural substance that stiffens the dynamic actin cytoskeleton in the organism. In the laboratory variant, the molecule was developed further, so that its structure changed when violet light was shined on it. This structural change increased the stabilizing effect of the molecule. After a certain period of time, or when a green light was shined on the molecule, its structure reverted to its inactive form and its natural dynamics were restored.

Partners in research: (from left) Florian Küllmer, Prof. Dr. Hans-Dieter Arndt, and Veselin Nasufovic in a laboratory at the University of Jena in Germany. Courtesy of Jürgen Scheere/FSU.

In experiments, the cell-permeable, photoswitchable molecules, called optojasps, were able to optically control the dynamics of the actin cytoskeleton and cellular functions that depended on it. After optojasps were absorbed by cells, the researchers could use light to control the viability and mobility of individual cells and cytoskeleton signaling with a high degree of spatial and temporal resolution. Individual cells could be selectively manipulated to a degree of accuracy of as little as 10 μm.

Looking ahead to potential future applications, Arndt said, “It is possible that this method could be used in the future to treat diseases of the eye or on the skin, that is, of organs that can easily be exposed to light. This technique could also be of interest in the field of neuroregeneration. The aim here is often to encourage certain nerve cells to grow in preference to others.” Arndt also believes there is potential to use the method in immune cells that are highly mobile.

With the optojasps substance, the influence of actin dynamics can be studied directly, Arndt said. “All you need to do is to add the compound and irradiate.” Arndt and his colleagues are working to optimize these molecules further and study them in greater detail.

The research was published in the Journal of the American Chemical Society (www. doi.org/10.1021/jacs.9b12898).