Over the past decades, chemists have extensively used molecular self-assembly as a bottom up approach to prepare well-ordered and truly sophisticated supramolecular architectures, many of which are able to exert specific functions. By exploiting the reversible nature of non-covalent interactions, great progress have been made in designing switchable, self-healing and self-replicating supramolecular systems that are able to change and adapt in response to external stimuli (e.g. light, pH, chemical modification, or enzymes). The latter have found exciting applications in catalysis, material science, and nanomedicine. Besides that, various kinetically trapped self-assembled structures have been obtained under kinetic control by rationally selecting the desired aggregation pathway. However, in spite of their remarkable structural complexity and responsiveness, artificial self-assembled systems lack the functional complexity that is the hallmark of living self-organized systems such as microtubules, ribosomes and biomembranes. This is because artificial self-assemblies evolve until a global (or local) free energy minimum is reached, after which they remain inactive. In other words, they reside either in thermodynamic equilibrium or kinetically trapped states. Living systems, on the other hand, continuously avoid equilibrium states, and are able to do so for extended periods of time, through a constant influx of energy. They reside in so-called dissipative non-equilibrium steady states, and continuously consume energy to keep their structure and function. The latter is at the bases of intricate biological functions, such as cell motility, muscle contraction, intracellular transport, and mitosis. For example, cells use fuel molecules like adenosine triphosphate (ATP) to control when and where supramolecular polymers such as actin should assemble and disassemble. Recently, artificial fuel-driven assemblies have been developed, in which the system can be pushed transiently out of equilibrium by addition of a chemical fuel, but then slowly relax towards its equilibrium states. Moreover, these systems can be refuelled, resulting in a new cycle of transient assembly, but the accumulation of waste from the fuel conversion, leads to a poisoning of the system, and to a limited number of possible cycles.
The aim of this project has been to realise non-equilibrium self-assembled steady states (NESS) of a supramolecular polymer, controlled by competitive enzymatic phosphorylation/dephosphorylation of the building blocks, in which the supramolecular assemblies are pushed and kept out of equilibrium by continuous influx of the chemical fuel ATP, and removal of waste through a membrane reactor.
Maintaining NESS conditions of a self-assembled system is a crucial advancement in the field of supramolecular chemistry, which will open the door to truly functional “living” systems.
At the end of the action, the proposed objectives were fully achieved, and we could successfully demonstrate that it is possible to keep supramolecular polymers in different NESS depending on the influx of chemical fuel supplied, and outflux of waste under continuous flow conditions.
