Lipidoid Artificial Compartments for Bidirectional Regulation of Enzyme Activity through Nanomechanical Action

Photoresponsive inhibitor and noninhibitor systems have been developed to achieve on-demand enzyme activity control. However, inhibitors are only effective for a specific and narrow range of enzymes. Noninhibitor systems usually require mutation and modification of the enzymes, leading to irreversible loss of enzymatic activities. Inspired by biological membranes, we herein report a lipidoid-based artificial compartment composed of azobenzene (Azo) lipidoids and helper lipids, which can bidirectionally regulate the activity of the encapsulated enzymes by light. In this system, the reversible photoisomerization of Azo lipidoids triggered by UV/vis light creates a continuous rotation-inversion movement, thereby enhancing the permeability of the compartment membrane and allowing substrates to pass through. Moreover, the membrane can revert to its impermeable state when light is removed. Thus, enzyme activity can be switched on and off when encapsulating enzymes in the compartments. Importantly, since neither mutation nor modification is required, negligible loss of activity is observed for the encapsulated enzymes after repeated activation and inhibition. Furthermore, this approach provides a generic strategy for controlling multiple enzymes by forgoing the use of inhibitors and may broaden the applications of enzymes in biological mechanism research and precision medicine.