Speaker
Description
Metabolic processes are crucial for sustaining life, involving the cyclic synthesis (anabolism) and degradation (catabolism) of chemical and supramolecular structures through the expense of chemical energy [1]. These highly dynamic structures which form under out-of-equilibrium (OOE) conditions define the hallmark features of life such as adaptivity and spatiotemporal control [2]. At the cellular level, metabolic activities govern functions by modulating phospholipid synthesis and breakdown. However, replicating synthetic vesicles that mimic cellular phospholipid membranes has proven difficult. In this work, we present a bioinspired approach for the in situ synthesis of biomimetic phospholipids and their self-assembly, driven by chemical fuel under physiological conditions, resulting in vesicles with a controllable lifetime. The phospholipids are formed via an amino-ester bond through imine formation (anabolic reaction), leading to spontaneous vesicle formation. In the presence of lipase, the ester bond is hydrolysed (catabolic reaction), triggering vesicle disassembly. Spectroscopic and microscopic analysis confirmed the continuous cycle of vesicle formation and breakdown. By varying lipase concentrations, we fine-tuned the vesicles’ lifetimes, ranging from minutes to hours. Additionally, by supplying excess fuel, we sustained these dynamic vesicles in its assembly state. Detailed studies showed that the assembly can be temporally controlled by the amount of fuel supplied as well as the kinetics of the enzymatic reaction. We also demonstrated the potential application of these vesicles for drug release by encapsulating hydrophobic and hydrophilic model drugs and showed that the release kinetics of the encapsulated cargo molecules can be dynamically regulated for potential applications in adaptive nanomedicine.
