Regulation of enzyme activity is key to the adaptation of cellular processes such as signal transduction and metabolism in response to varying external conditions. Synthetic molecular glues have provided effective systems for enzyme inhibition and regulation of protein-protein interactions. So far, all the molecular glue systems based on covalent interactions operated in equilibrium conditions. To emulate dynamic far-from-equilibrium biological processes, we introduce herein a transient supramolecular glue with controllable lifetime. The transient system uses multivalent supramolecular interactions between guanidium group-bearing surfactants and adenosine triphosphates (ATP), resulting in bilayer vesicle structures. Unlike the conventional fuels for non-equilibrium 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. We further demonstrate temporal activation and control of biocatalytic cascade networks on the vesicles, which represents an essential cellular component. 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.
A Dissipative Supramolecular Glue for Temporal Control of Amplified Enzyme Activity and Biocatalytic Cascades
14 November 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.