Homogeneous hybrid droplet interface bilayers assembled from binary mixtures of DPhPC phospholipids and PB-b-PEO diblock copolymers.

Hybrid membranes built from phospholipids and amphiphilic block copolymers seek to capitalize on the benefits of both constituents for constructing biomimetic interfaces with improved performance. However, hybrid membranes have not been formed or studied using the droplet interface bilayer (DIB) method, an approach that offers advantages for revealing nanoscale changes in membrane structure and mechanics and offers a path toward assembling higher-order tissues. We report on hybrid droplet interface bilayers (hDIBs) formed in hexadecane from binary mixtures of synthetic diphytanoyl phosphatidylcholine (DPhPC) lipids and low molecular weight 1,2 polybutadiene-b-polyethylene oxide (PBPEO) amphiphilic block copolymers and use electrophysiology measurements and imaging to assess the effects of PBPEO in the membrane. This work reveals that hDIBs containing up to 15 mol% PBPEO plus DPhPC are homogeneously mixtures of lipids and polymers, remain highly resistive to ion transport, and are stable-including under applied voltage. Moreover, they exhibit hydrophobic thicknesses similar to DPhPC-only bilayers, but also have significantly lower values of membrane tension. These characteristics coincide with reduced energy of adhesion between droplets and the formation of alamethicin ion channels at significantly lower threshold voltages, demonstrating that even moderate amounts of amphiphilic block copolymers in a lipid bilayer provide a route for tuning the physical properties of a biomimetic membrane.

Memristive plasticity in artificial electrical synapses via geometrically reconfigurable, gramicidin-doped biomembranes.

It is now known that mammalian brains leverage plasticity of both chemical and electrical synapses (ES) for collocating memory and processing. Unlike chemical synapses, ES join neurons via gap junction ion channels that permit fast, threshold-independent, and bidirectional ion transport. Like chemical synapses, ES exhibit activity-dependent plasticity, which modulates the ionic conductance between neurons and, thereby, enables adaptive synchronization of action potentials. Many types of adaptive computing devices that display discrete, threshold-dependent changes in conductance have been developed, yet far less effort has been devoted to emulating the continuously variable conductance and activity-dependent plasticity of ES. Here, we describe an artificial electrical synapse (AES) that exhibits voltage-dependent, analog changes in ionic conductance at biologically relevant voltages. AES plasticity is achieved at the nanoscale by linking dynamical geometrical changes of a host lipid bilayer to ion transport via gramicidin transmembrane ion channels. As a result, the AES uniquely mimics the composition, biophysical properties, bidirectional and threshold-independent ion transport, and plasticity of ES. Through experiments and modeling, we classify our AES as a volatile memristor, where the voltage-controlled conductance is governed by reversible changes in membrane geometry and gramicidin channel density. Simulations show that AES plasticity can adaptively synchronize Hodgkin-Huxley neurons. Finally, by modulating the molecular constituents of the AES, we show that the amplitude, direction, and speed of conductance changes can be tuned. This work motivates the development and integration of ES-inspired computing devices for achieving more capable neuromorphic hardware.

Electrophysiological interrogation of asymmetric droplet interface bilayers reveals surface-bound alamethicin induces lipid flip-flop.

The droplet interface bilayer (DIB) method offers simple control over initial leaflet compositions in model membranes, enabling an experimental path to filling gaps in our knowledge about the interplay between compositional lipid asymmetry, membrane properties, and the behaviors of membrane-active species. Yet, the stability of lipid leaflet asymmetry in DIBs has received very little attention, particularly in the presence of peptides and ion channels that are often studied in DIBs. Herein, we demonstrate for the first time parallel, capacitance-based measurements of intramembrane potential with arrays of asymmetric DIBs assembled in a microfluidic device to characterize the stability of leaflet asymmetry over many hours in the presence and absence of membrane-active peptides. DIBs assembled from opposing monolayers of the ester (DPhPC) and ether (DOPhPC) forms of diphytanoyl-phosphatidylcholine yielded asymmetric bilayers with leaflet compositions that were stable for at least 18 h as indicated by a stable |137 mV| intramembrane potential. In contrast, the addition of surface-bound alamethicin peptides caused a gradual, concentration-dependent decrease in the magnitude of the dipole potential difference. Intermittent current-voltage measurements revealed that alamethicin in asymmetric DIBs also shifts the threshold voltage required to drive peptide insertion and ion channel formation. These outcomes take place over the course of 1 to 5 h after membrane formation, and suggest that alamethicin peptides promote lipid flip-flop, even in the un-inserted, surface-bound state, by disordering lipids in the monolayer to which they bind. Moreover, this methodology establishes the use of parallel electrophysiology for efficiently studying membrane asymmetry in arrays of DIBs.