Demolish and Rebuild: Controlling Lipid Self-Assembly toward Triggered Release and Artificial Cells

The ability to modulate the structures of lipid membranes, predicated on our nuanced understanding of the properties that drive and alter lipid self-assembly, has opened up many exciting biological applications. In this Perspective, we focus on two endeavors in which the same principles are invoked to achieve completely opposite results. On one hand, controlled liposome decomposition enables triggered release of encapsulated cargo through the development of synthetic lipid switches that perturb lipid packing in the presence of disease-associated stimuli. In particular, recent approaches have utilized artificial lipid switches designed to undergo major conformational changes in response to a range of target conditions. On the other end of the spectrum, the ability to drive the in situ formation of lipid bilayer membranes from soluble precursors is an important component in the establishment of artificial cells. This work has culminated in chemoenzymatic strategies that enable lipid manufacturing from simple components. Herein, we describe recent advancements in these two unique undertakings that are linked by their reliance on common principles of lipid self-assembly.