A transient vesicular glue for amplification and temporal regulation of biocatalytic reaction networks.

Regulation of enzyme activity and biocatalytic cascades on compartmentalized cellular components is key to the adaptation of cellular processes such as signal transduction and metabolism in response to varying external conditions. Synthetic molecular glues have enabled enzyme inhibition and regulation of protein-protein interactions. So far, all the molecular glue systems based on covalent interactions operated under steady-state conditions. To emulate dynamic biological processes under dissipative conditions, we introduce herein a transient supramolecular glue with a controllable lifetime. The transient system uses multivalent supramolecular interactions between guanidinium group-bearing surfactants and adenosine triphosphate (ATP), resulting in bilayer vesicle structures. Unlike the conventional chemical agents for dissipative assemblies, ATP here plays the dual role of providing a structural component for the assembly as well as presenting active functional groups to "glue" enzymes on the surface. While gluing of the enzymes on the vesicles achieves augmented catalysis, oscillation of ATP concentration allows temporal control of the catalytic activities similar to the dissipative cellular nanoreactors. We further demonstrate temporal upregulation and control of complex biocatalytic reaction networks on the vesicles. Altogether, the temporal activation of biocatalytic cascades on the dissipative vesicular glue presents an adaptable and dynamic system emulating heterogeneous cellular processes, opening up avenues for effective protocell construction and therapeutic interventions.