Enlightening cell migration through the development and applications of photoresponsive molecules to remodel actin networks – SwitchActin

The actin cytoskeleton controls cell shape and motility. A myriad of actin-binding proteins govern the polymerization of globular actin into filaments. To study the role of the actin cytoskeleton in various biological processes, natural and synthetic small molecules are used by biologists. Besides, breakthrough technologies involving photo-inducible compounds allow accurate controls of biological processes in time and space by light. In that context, our interdisciplinary proposal aims at developing a toolbox of photoinducible chemical inhibitors targeting filament nucleation, elongation and branching as well as myosin mediated contractility, to decipher the complex relationships between dynamic remodeling of actin networks and cell migration. Three teams involving synthetic chemists, biochemists and cell biologists will participate to this global aim, with three essential tasks: (1) design and synthesis of light-inducible chemical tools; (2) development of the control of actin dynamics by these compounds in vitro; (3) characterization of lamellipodium dynamics in treated cells and control of cell migration. The orthogonal control of actin dynamics, in space and time by various photo-activatable compounds sensitive to different wavelengths, is expected to mimic the activity of signaling pathways that control cell migration.