Detection of Ganglioside-Specific Toxin Binding with Biomembrane-Based Bioelectronic Sensors

Abstract

Gangliosides, glycolipids that are abundant in the plasma membrane outer leaflet, play an integral role in cellular recognition, adhesion, and infection by interacting with different endogenous molecules, viruses, and toxins. Model membrane systems, such as ganglioside-enriched supported lipid bilayers (SLBs), present a useful tool for sensing, characterizing, and quantifying such interactions. In this work, we report the formation of ganglioside GM1-rich SLBs on conducting polymer electrodes using a solvent-assisted lipid bilayer assembly method to investigate changes in membrane electrical properties upon binding of the B subunit of cholera toxin. The sensing capabilities of our platform were investigated by varying both the receptor and the toxin concentrations in the system as well as using a complex sample (milk contaminated with the toxin) and monitoring the changes in the electrical properties of the membrane. Our work highlights the potential of such conducting polymer-supported biomembrane-based platforms for detecting the toxins within a complex environment, studying ganglioside-specific biomolecular interactions with toxins and screening inhibitory molecules to prevent these interactions.

Organic Bioelectronics for In Vitro Systems

“…(Figure 28) 251,379 Very recently, this technology was implemented for fundamental understanding of membrane events governed by infection processes including virus− membrane interactions, 380 as well as toxin binding. 381 3.2. 2D Cell Cultures 3.2.1.…”

“…This method can therefore readily serve as an alternative to patch clamp whole cell experiments. (Figure ) , Very recently, this technology was implemented for fundamental understanding of membrane events governed by infection processes including virus–membrane interactions, as well as toxin binding …”

Process Engineering and Glycosyltransferase Improvement for Short Route Chemoenzymatic Total Synthesis of GM1 Gangliosides

“…Specific ganglioside‐binding domains (GBDs) have been identified in a diverse array of proteins including neurotransmitter receptors, bacterial toxins, viral surface proteins, and proteins involved in various neurodegenerative diseases [8] . GM1 is a well‐known cell surface receptor for pentameric cholera toxin B‐subunits [9] and has been used to develop biosensors [10] . SARS‐CoV‐2 receptor binding domain (RBD) was also shown to bind to GM1, GM2, and GM3 [11] .…”

Cell-Free Synthesis Goes Electric: Dual Optical and Electronic Biosensor via Direct Channel Integration into a Supported Membrane Electrode

“…Supported lipid bilayers (SLB) assembled on the surface of conducting polymers provide a unique solution to couple TMP activity with electronic interfaces . SLBs are planar, supported membranes that are compatible with various surface analytical techniques. − Importantly, SLBs can be used to coat electrodes with a lipid membrane to translate biological activity into electrical readouts. ,− While the direct deposition of cell membranes on PEDOT surfaces has provided a promising strategy to interface lipid bilayers and TMPs onto electronically active materials, , biological membranes are highly complex, which can confound measurement signals. Additionally, these methods can have a lengthy development timeline, are often costly, and require specialized equipment and reagents.…”