Immune cells exhibit stimulation-dependent traveling waves in the cortex, much faster than typical cortical actin waves. These waves reflect rhythmic assembly of both actin machinery and peripheral membrane proteins such as F-BAR domain-containing proteins. Combining theory and experiments, we develop a mechanochemical feedback model involving membrane shape changes and F-BAR proteins that render the cortex an interesting dynamical system. We show that such cortical dynamics manifests itself as ultrafast traveling waves of cortical proteins, in which the curvature sensitivity-driven feedback always constrains protein lateral diffusion in wave propagation. The resulting protein wave propagation mainly reflects the spatial gradient in the timing of local protein recruitment from cytoplasm. We provide evidence that membrane undulations accompany these protein waves and potentiate their propagation. Therefore, membrane shape change and protein curvature sensitivity may have underappreciated roles in setting high-speed cortical signal transduction rhythms.

Membrane curvature has emerged as an intriguing physical principle underlying biological signaling and membrane trafficking. The CIP4/FBP17/Toca-1 F-BAR subfamily is unique in the BAR family because its structurally folded F-BAR domain does not contain any hydrophobic motifs that insert into membrane. Although widely assumed so, whether the banana-shaped F-BAR domain alone can sense curvature has never been experimentally demonstrated. Using a nanobar-supported lipid bilayer system, we found that the F-BAR domain of FBP17 displayed minimal curvature sensing in vitro. In comparison, an alternatively spliced intrinsically disordered region (IDR) adjacent to the F-BAR domain has the membrane curvature-sensing ability greatly exceeding that of F-BAR domain alone. In living cells, the presence of the IDR delayed the recruitment of FBP17 in curvature-coupled cortical waves. Collectively, we propose that contrary to the common belief, FBP17's curvature-sensing capability largely originates from IDR, and not the F-BAR domain alone.

The platform reported here is a powerful tool for studying mechanically induced physiological changes in cells. Such a device could be used in tissue regeneration for maintaining essential cell growth conditions.

Membrane curvature has been recognized as an active participant of fundamental biological processes including vesicular transport and organelle biogenesis, but its effects on membrane remodeling are typically local. Here we show membrane curvature plays a critical role in propagating cortical waves and modulating mesoscale dynamics in living cells. We employ a membrane shape-dependent mechanochemical feedback model to account for the observed oscillatory travelling waves of Cdc42, F-BAR proteins and actin.We demonstrate that oscillatory membrane shape changes accompany and are required for such spatiotemporal patterns. In addition, modulating the curvature preference of the F-BAR proteins or membrane tension perturbs wave propagation. Our findings identify a distinct role of membrane curvature in mediating collective dynamics of cortical proteins and provide a molecular framework for integrating membrane mechanics and biochemical signaling in the context of subcellular pattern formation.