Facile Generation of Biomimetic-Supported Lipid Bilayers on Conducting Polymer Surfaces for Membrane Biosensing

Abstract

Membrane biosensors that can rapidly sense pathogen interaction and disrupting agents are needed to identify and screen new drugs to combat antibiotic resistance. Bioelectronic devices have the capability to read out both ionic and electrical signals, but their compatibility with biological membranes is somewhat limited. Supported lipid bilayers (SLBs) have served as useful biomimetics for a myriad of research topics involving biological membranes. However, SLBs are traditionally made on inert, rigid, inorganic surfaces. Here, we demonstrate a versatile and facile method for generating SLBs on a conducting polymer device using a solvent-assisted lipid bilayer (SALB) technique. We use this bioelectronic device to form both mammalian and bacterial membrane mimetics to sense the membrane interactions with a bacterial toxin (α-hemolysin) and an antibiotic compound (polymyxin B), respectively. Our results show that we can form high quality bilayers of both types and sense these particular interactions with them, discriminating between pore formation, in the case of α-hemolysin, and disruption of the bilayer, in the case of polymyxin B. The SALB formation method is compatible with many membrane compositions that will not form via common vesicle fusion methods and works well in microfluidic devices. This, combined with the massive parallelization possible for the fabrication of electronic devices, can lead to miniaturized multiplexed devices for rapid data acquisition necessary to identify antibiotic targets that specifically disrupt bacterial, but not mammalian membranes, or identify bacterial toxins that strongly interact with mammalian membranes.

Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology

“…These have shown to be more robust and stable than previously developed model membranes owning their stability to the localized tight lipids packing and the solid supporting scaffold. Their robustness and stability lead to their popularity in molecular electronic microfluidic chips [ 14 , 86 , 87 ]. They were first introduced by Tamm and McConnell, where two water-air monolayers were deposited on a hydrophilic solid support such as silicon, glass and quartz [ 88 ].…”

Shining Light on Human Gut Bacteriophages

“…With this, it is possible to mimic bacterial and mammalian membranes, called supported lipid bilayers, using bioelectronic tools and membrane biosensors which can detect specific interactions. For example, this method was used to examine membrane interactions with antibiotics to determine antibiotic targets that were discriminatory between bacterial and mammalian membranes (Su et al, 2019 ). Similar tools were used to monitor Salmonella typhimurium infection of epithelial cells (Tria et al, 2014 ).…”

A conjugated polymer‐liposome complex: A contiguous water‐stable, electronic, and optical interface

“…[ 18–23 ] In addition, a recent research direction explores interfacing supported lipid bilayers (SLBs) with a conductive film based on conjugated polymers with promising results. [ 24–29 ] Thus, we present a brief overview on the origin of the electronic and optical properties of these polymers.…”

“…A promising new approach that further demonstrates the utility of interfacing conjugated polymers with liposomes is investigating SLBs supported by the conjugated polymer when used as an active channel in an organic electrochemical transistor. [ 24–28,54,55 ] Here, the conjugated polymer establishes an electronic communication with the membrane and is an electric read‐out, revealing changes in the permeability and morphology of the SLB. This is a promising platform shown to identify bacterial toxins or antibiotic targets that disrupt bacteria, [ 27 ] elucidate the interaction of compounds [ 26 ] and insertion of proteins with the membrane, [ 25 ] monitor ion channel activity in complex biological SLBs [ 28 ] and in SLBs incorporating gramicidin channel.…”