Existing cell-cell communication systems are limited by message-channel coupling. Four alternate schemes for engineering cell-cell communication. Gray circles represent cells. Colored arcs on left cells represent transmitters with different colors representing distinct transmitters. Stick-drawings on right cells depict receivers. Icons passing between cells represent information channels with colors representing distinct messages. (a) Single channel coupled to specific message (e.g., AHL-based systems), (b) Single channel coupled to specific message but with multiple receivers (e.g., AHL-based systems in which signaling molecule is recognized by distinct cognate response factors), (c) Multiple insulated channels each coupled to a specific message (e.g., a set of AHL-based systems with no crosstalk between signaling molecules and cognate response factors), (d) Single channel decoupled from any one message (e.g., M13-based systems, this work).