Pattern generation with synthetic sensing systems in lipid bilayer membranes

Abstract

The objective of this study was to introduce differential sensing techniques to synthetic systems that act, like olfactory receptors, as transporters in lipid bilayer membranes. Routine with most alternative chemosensing ensembles, pattern generation has, quite ironically, remained inaccessible in lipid bilayers because the number of available crossresponsive sensor components has been insufficient. To address this challenge, we here report on the use of cationic hydrazides that can react in situ with hydrophobic analytes to produce cationic amphiphiles which in turn can act as countercation activators for polyanionic transporters in fluorogenic vesicles. To expand the dimension of signals generated by this system, a small collection of small peptides containing a positive charge (guanidinium, ammonium) and one to three reactive hydrazides are prepared. Odorants are used as examples for hydrophobic analytes, perfumes to probe compatibility with complex matrices, and counterion-activated calf-thymus DNA as representative polyion–counterion transport system. Principal component and hierarchical cluster analysis of the obtained multidimensional patterns are shown to differentiate at least 21 analytes in a single score plot, discriminating also closely related structures such as enantiomers, cis–trans isomers, single-atom homologs, as well as all tested perfumes. Inverse detection provides access to analytes as small as acetone. The general nature of the introduced methodology promises to find diverse applications in current topics in biomembrane research

Dynamic Octopus Amphiphiles as Powerful Activators of DNA Transporters: Differential Fragrance Sensing and Beyond

“…[27] Without modification, these analytes are essentially undetectable with most synthetic sensing systems that operate in lipid bilayer membranes. However, their incubation with cations G1H1-G1H3 and A1H1-A1H3 that contain at least one hydrazide gives hydrazones, such as G1H1O1-G1H3O13, and A1H1O1-A1H3O13, which in turn can activate polyanions, such as calf thymus DNA (ctDNA) as cation transporter in fluorogenic vesicles (Figures 1 and Scheme 1).…”

“…[27] Incubation of analytes with different reactive counterions produces a small collection of in-/activators of synthetic transport systems (Figure 1). From the fluorescent response to increasing activator concentrations, characteristics, such as the maximum normalized response as determined after 190 s (Y MAX ), the effective concentration to reach 50 % of this maximal activity (EC 50 ), or the Hill coefficient (n) are extracted to generate analyte specific patterns.…”

“…[3,4] To overcome this limitation, we have considered the following sensing scheme. [27] Hydrophobic analytes, otherwise undetectable with membrane-based sensing systems, are first covalently captured by reactive hydrophilic cations ( Figure 1). The resulting amphiphiles can act as countercation activators for polyanions and generate active polyion-counterion transport systems.…”

“…[1] To get there, we have recently introduced pattern recognition to synthetic systems that work in lipid bilayer membranes ( Figure 1). [27] In pattern recognition or "differential" sensing approaches, single analytes are identified and quantified not from molecular recognition by one specific sensor but as a unique composite response or fingerprint. [28][29][30][31][32][33][34][35][36][37][38][39][40] Pattern recognition is attractive for signal generation because promiscuous behavior of individual sensors is not only tolerated but preferable, and an infinite number of analytes can be detected with a relatively small number of individual sensing units.…”

Advances in Minimal Cell Models: a New Approach to Synthetic Biology and Origin of Life

“…different kind of molecules. An interesting study on the use of lipid vesicles for sensing odorants has been reported (Takeuchi et al, 2011). Although the core mechanism was based on chemical transformation, it is possible to think to similarly working biomolecular networks.…”