Abstract
In biology, membrane-spanning proteins are responsible for the transmission of chemical signals across membranes, including the signal recognition-mediated conformational change of transmembrane receptors at the cell surface, and a trigger of an intracellular phosphorylation cascade. The ability to reproduce such biological processes in artificial systems has potential applications in smart sensing, drug delivery, and synthetic biology. Here, an artificial transmembrane receptors signaling system was designed and constructed based on modular DNA scaffolds. The artificial transmembrane receptors in this system are composed of three functional modules: signal recognition, lipophilic transmembrane linker, and signal output modules. Adenosine triphosphate (ATP) served as an external signal input to trigger the dimerization of two artificial receptors on membranes through a proximity effect. This effect induced the formation of a G-quadruplex, which served as a peroxidase-like enzyme to facilitate a signal output measured by either fluorescence or absorbance in the lipid bilayer vesicles. The broader utility of this modular method was further demonstrated using a lysozyme-binding aptamer instead of an ATP-binding aptamer. Therefore, this work provides a modular and generalizable method for the design of artificial transmembrane receptors. The flexibility of this synthetic methodology will allow researchers to incorporate different functional modules while retaining the same molecular framework for signal transduction.