A Photocaged Microtubule-Stabilising Epothilone allows Spatiotemporal Control of Cytoskeletal Dynamics

The cytoskeleton is essential for spatial and temporal organization of a wide range of cellular and tissue-level processes, such as proliferation, signalling, cargo transport, migration, morphogenesis, and neuronal development. Cytoskeleton research aims to study these processes by imaging, or by locally manipulating, the dynamics and organisation of cytoskeletal proteins with high spatiotemporal resolution: which matches the capabilities of optical methods. To date, no photoresponsive microtubule-stabilising tool has united all the features needed for a practical high-precision reagent: i.e., a low potency and biochemically stable non-illuminated state; then efficient, rapid, and clean photoresponse that generates a high potency illuminated state; and good solubility at suitable working concentrations; and efficient synthetic access. We now present CouEpo, a photocaged epothilone microtubule-stabilizing reagent, that combines these needs. Its potency increases ~100-fold upon violet/blue irradiation to reach low-nanomolar values, allowing efficient photocontrol of microtubule dynamics in live cells, and even generation of cellular asymmetries in microtubule architecture and cell dynamics. CouEpo is thus a high-performance tool compound that can support high-precision research into many microtubule-associated processes, from biophysics to transport, cell motility, and neuronal physiology.