A kinase-responsive synthetic ion channel

Synthetic ion channels that imitate biological counterparts have become increasingly important in synthetic biology and the recently emerging field of engineering biology. Recent advances have yielded channels that are responsive to various stimuli, including light, voltage, ligands, pH, temperature, and mechanical forces. However, designing channels that react to biologically relevant enzyme activity remains challenging. Here, we report a synthetic ion channel triggered by cAMP-dependent protein kinase (PKA) to modulate ion transport across lipid bilayers. This channel is assembled modularly from two subunits: a metal-organic polyhedron (MOP)-based core and a shell of kinase-responsive peptides featuring a kemptide moiety. Single-channel electrophysiological recordings demonstrate that PKA-mediated phosphorylation of the kemptide enhances ion transport activity. When embedded in HeLa cell membranes, these channels are activated by PKA and elevate Ca²⁺ influx, resulting in a 48 % reduction of cell growth after 24 h. This enzyme-responsive design provides a strategy for integrating the activity of synthetic ion channels with phosphorylation-driven signaling pathways.