Optical Control of the Actin Cytoskeleton

Project Summary/Abstract The goal of this project is the optical control of the actin cytoskeleton with photoswitchable molecules. These compounds target monomeric G-actin, polymeric F-actin, the nucleator complex Arp2/3, and the motor protein myosin II. Our probes aimed at F-actin and G-actin are derived from the natural products jasplakinolide, yielding opto-Jasp, cytochalasin D (opto-Chal), and latrunculin B (opto-Lat), respectively. The photoswitchable molecules for Arp2/3 stem from CK-666 (opto-CK) and the photoswitchable myosin 2 inhibitors from blebbistatin and similar compounds (opto-MI). We have already obtained significant preliminary results in a variety of cells (e.g. yeast, HeLa, neurons, oligodendrocytes, microglia). Our proposed program constitutes the continuation of our long-standing and successful program on optically controlling actin and tubulin, as well as associated motor proteins with photoswitchable small molecules. The close collaboration between a chemical biologist and a structural biologist will yield useful probes that are shared with the community and could form the basis of a new form of precision chemotherapeutics.