ATP‐Mediated Bidirectional Communication Between Natural and Artificial Cells for Controlled Bioreactions

ABSTRACT Communication between living and artificial cells represents a fundamental step toward constructing hybrid systems capable of cooperative behaviors. Here, we introduce an ATP‐mediated energy transduction mechanism that enables bidirectional communication between natural dendritic cells and stimuli‐responsive polymersome artificial cells. The polymersomes were equipped with a photo‐switchable spiropyran derivative, which provides light‐gated control of membrane permeability. Upon UV irradiation, the membrane transiently increases permeability, allowing ATP transport across the boundary. This enables signal transduction from natural cells to artificial ones, demonstrated by ATP uptake triggering internal coacervation and the ATP‐dependent firefly luciferase reaction inside polymersomes. Conversely, artificial cells containing ATP or the pyruvate kinase enzyme release ATP to surrounding dendritic cells, resulting in increased intracellular calcium levels. The system thus establishes a reciprocal molecular dialogue via energy uptake and signal generation from natural to artificial cells, and metabolic stimulation from artificial to natural cells. This study provides a robust platform for dynamic cell‐material interaction and controlled biochemical communication, advancing artificial and living cell integration toward engineered signaling interfaces and programmable bio‐hybrid systems.