Hybrid Supported Lipid Bilayers for Bioinspired Bioelectronics with Enhanced Stability

Abstract

A promising new class of biosensors leverages the sensing mechanisms of living cells by incorporating native transmembrane proteins into biomimetic membranes. Conducting polymers (CPs) can further improve the detection of electrochemical signals from these biological recognition elements through their low electrical impedance. Supported lipid bilayers (SLBs) on CPs mimic the structure and biology of the cell membrane to enable such sensing, but their extrapolation to new target analytes and healthcare applications has been difficult due to their poor stability and limited membrane properties. Blending native phospholipids with synthetic block copolymers to create a hybrid SLB (HSLB) may address these challenges by allowing for the tuning of chemical and physical properties during membrane design. We establish the first example of HSLBs on a CP device and show that polymer incorporation enhances bilayer resilience and thus offers important benefits toward bio-hybrid bioelectronics for sensing applications. Importantly, HSLBs outperform traditional phospholipid bilayers in stability by exhibiting strong electrical sealing after exposure to physiologically relevant enzymes that cause phospholipid hydrolysis and membrane degradation. We investigate the impact of HSLB composition on membranes and device performance and demonstrate the ability to finely adjust the lateral diffusivity of HSLBs with modest changes in block copolymer content through a large compositional range. The inclusion of the block copolymer into the bilayer does not disrupt electrical sealing on CP electrodes, an essential metric for electrochemical sensors, or the insertion of a representative transmembrane protein. This work interfacing tunable and stable HSLBs with CPs paves the way for future bioinspired sensors that combine the exciting developments from both bioelectronics and synthetic biology.

Design and Construction of a Multi-Tiered Minimal Actin Cortex for Structural Support in Lipid Bilayer Applications

“…These combined functions make actin appropriate for applications in which the molecular properties of lipids and mechanical stability are important. Artificial supports for bilayers mimic the role of the cellular cytoskeleton and are employed throughout biophysics, biomaterials, and bioengineering research, offering a platform for studying membrane properties, cell signaling, membrane–protein interactions, and bilayer functionalization. − Numerous strategies have been developed, such as forming bilayers on hydrated polymer cushions, tethering the bilayer to solid surfaces or microcavities, trapping the bilayer between two hydrogel layers, photopolymerizing reactive amphiphiles in the lipid membrane, cross-linking lipid molecules comprising the bilayer, and polymerizing actin within liposomes …”

Droplet Polymer Bilayers for Bioelectronic Membrane Interfacing

“…SLBs on solid supports generally have a lower membrane resistance (1 kΩ cm 2 to 1 MΩ cm 2 ) because of interactions with the underlying substrate. , Further, while soft, hygroscopic polymer substrates can cushion fluid membranes, their rough surfaces can dissuade SLB formation and generate new sources of membrane defects. − Previous works creating SLBs on conducting polymers have innovated in polymer surface treatments − and membrane formation techniques to overcome this barrier. Despite this, SLBs on conducting polymer electrodes have displayed particularly low electrical sealing to nonspecific ionic currents, with normalized membrane resistances of <1 kΩ*cm 2 , suggesting incomplete surface coverage and the presence of significant membrane defects that may hinder future investigation of ion transport processes. ,,,− …”