Triggered Release from Lipid Bilayer Vesicles by an Artificial Transmembrane Signal Transduction System

Abstract

The on-demand delivery of drug molecules from nano-scale carriers with spatio-temporal control is a key challenge in modern medicine. Here we show that lipid bilayer vesicles (liposomes) can be triggered to release an encapsulated molecular cargo in response to an external control signal by employing an artificial transmembrane signal transduction mechanism. A synthetic signal transducer embedded in the lipid bilayer membrane acts as a switchable catalyst, catalyzing the formation of surfactant molecules inside the vesicle in response to a change in external pH. The surfactant permeabilises the lipid bilayer membrane to facilitate release of an encapsulated hydrophilic cargo. In the absence of the pH control signal, the catalyst is inactive and the cargo remains encapsulated within the vesicle.

Apoptosis-inducing activity of a fluorescent barrel-rosette M+/Cl− channel

“…28 To investigate the integrity of the membrane aer addition of 1d or the formation of supramolecular pores in the membrane, the leakage of carboxyuorescein (CF) was monitored across EYPC-LUVsICF. 55 It is well known that a high concentration of CF molecules inside the liposomes leads to the uorescence quenching of the dye due to collisions among the molecules. However, efflux of these molecules from the liposomes into the external buffer restores their uorescence (l em ¼ 517 nm, l ex ¼ 492 nm).…”

Membrane functionalization in artificial cell engineering

“…Unlike living systems which rely on proteins for almost all functions, ACs are readily compatible with the wide range of molecules generated by synthetic chemistry and nanotechnology. These include synthetic block polymer ion channels [115] and DNA origami nanopores [116,117] to replace the use of membrane protein pores, the creation of hybrid copolymer-lipid membranes for patterning and increased membrane stability [118,119], nucleic acid cytoskeletons [120], synthetic molecules capable of signal transduction across the AC membrane without the use of protein components [121,122] and nucleic acid strand displacement networks to program cell functions [123][124][125][126]. One future challenge to be considered if using synthetic molecules instead of biologically derived components in ACs is how to integrate regeneration of such components in situ without destabilising the cell itself.…”

Supramolecular Chemistry in the Biomembrane

“…It would be interesting to see whether signal transduction still proceeded, if the vesicles were prepared with an excess of internal Cu 2+ : assuming an exclusive shuttling motion of the transducer would still give a signal transduction event, whereas a flipping motion of the transducer would orient the phen group inward, and binding with internal excess Cu 2+ would prevent the formation of the catalytically active zinc‐2,6‐diacetylpyridine dioxime complex. Finally, a very interesting extension of this work involved the 38⋅ Zn 2+ ‐mediated catalysis of a liposome‐encapsulated ester, which produced an amphiphilic carboxylic acid that made the lipid membrane sufficiently permeable to afford the triggered release of calcein from the vesicles …”