Droplet Polymer Bilayers for Bioelectronic Membrane Interfacing.

Model membranes interfaced with bioelectronics allow for the exploration of fundamental cell processes and the design of biomimetic sensors. Organic conducting polymers are an attractive surface on which to study the electrical properties of membranes because of their low impedance, high biocompatibility, and hygroscopic nature. However, establishing supported lipid bilayers (SLBs) on conducting polymers has lagged significantly behind other substrate materials, namely, for challenges in membrane electrical sealing and stability.

Simultaneous Electrophysiology and Imaging Reveal Changes in Lipid Membrane Thickness and Tension upon Uptake of Amphiphilic Gold Nanoparticles.

Amphiphilic gold core nanoparticles (AmNPs) striped with hydrophilic 11-mercapto-1-undecanesulfonate (MUS) and hydrophobic 1-octanethiol (OT) ligands are promising candidates for drug carriers that passively and nondisruptively enter cells. Yet, how they interact with cellular membranes is still only partially understood. Herein, we use electrophysiology and imaging to carefully assess changes in droplet interface bilayer lipid membranes (DIBs) incurred by striped AmNPs added via microinjection.

Entrapment and Voltage-Driven Reorganization of Hydrophobic Nanoparticles in Planar Phospholipid Bilayers.

Engineered nanoparticles (NPs) possess diverse physical and chemical properties, which make them attractive agents for targeted cellular interactions within the human body. Once affiliated with the plasma membrane, NPs can become embedded within its hydrophobic core, which can limit the intended therapeutic functionality and affect the associated toxicity. As such, understanding the physical effects of embedded NPs on a plasma membrane is critical to understanding their design and clinical use.

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.

Nanoparticle-Induced Disorder at Complex Liquid-Liquid Interfaces: Effects of Curvature and Compositional Synergy on Functional Surfaces.

The self-assembly of surfactant monolayers at interfaces plays a sweeping role in tasks ranging from household cleaning to the regulation of the respiratory system. The synergy between different nanoscale species at an interface can yield assemblies with exceptional properties, which enhance or modulate their function. However, understanding the mechanisms underlying coassembly, as well as the effects of intermolecular interactions at an interface, remains an emerging and challenging field of study.

Modeling the saturation of detergent association in mixed liposome systems.

Cells tune the lipid types present in their membranes to adjust for thermal and chemical stability, as well as to promote association and dissociation of small molecules and bound proteins. Understanding the influence of lipid type on molecule association would open doors for targeted cell therapies, in particular when molecular association is observed in the presence of competing membranes. For this reason, we modeled and experimentally observed the association of a small molecule with two membrane types present by measuring the association of the detergent Triton X-100 with two types of liposomes, egg phosphatidylcholine (ePC) liposomes and egg phosphatidic acid (ePA) liposomes, at varying ratios.

Temperature-Controlled Assembly and Characterization of a Droplet Interface Bilayer.

The droplet interface bilayer (DIB) method for assembling lipid bilayers (i.e., DIBs) between lipid-coated aqueous droplets in oil offers key benefits versus other methods: DIBs are stable and often long-lasting, bilayer area can be reversibly tuned, leaflet asymmetry is readily controlled via droplet compositions, and tissue-like networks of bilayers can be obtained by adjoining many droplets.

Author Correction: Artificial water channels enable fast and selective water permeation through water-wire networks.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Artificial water channels enable fast and selective water permeation through water-wire networks.

Artificial water channels are synthetic molecules that aim to mimic the structural and functional features of biological water channels (aquaporins). Here we report on a cluster-forming organic nanoarchitecture, peptide-appended hybrid[4]arene (PAH[4]), as a new class of artificial water channels. Fluorescence experiments and simulations demonstrated that PAH[4]s can form, through lateral diffusion, clusters in lipid membranes that provide synergistic membrane-spanning paths for a rapid and selective water permeation through water-wire networks.

A new approach for investigating the response of lipid membranes to electrocompression by coupling droplet mechanics and membrane biophysics.

A new method for quantifying lipid-lipid interactions within biomimetic membranes undergoing electrocompression is demonstrated by coupling droplet mechanics and membrane biophysics. The membrane properties are varied by altering the lipid packing through the introduction of cholesterol. Pendant drop tensiometry is used to measure the lipid monolayer tension at an oil-water interface.

Lipid shape determination of detergent solubilization in mixed-lipid liposomes.

The effects of lipid charge and head group size on liposome partitioning by detergents is an important consideration for applications such as liposomal drug delivery or proteoliposome formation. Yet, the solubilization of mixed-lipid liposomes, those containing multiple types of lipids, by detergents has received insufficient attention. This study examines the incorporation into and subsequent dissolution of mixed-lipid liposomes comprised of both egg phosphatidylcholine (ePC) and egg phosphatidic acid (ePA) by the detergent Triton-X100 (TX).

Insight into the Mechanisms Driving the Self-Assembly of Functional Interfaces: Moving from Lipids to Charged Amphiphilic Oligomers.

Polymer-stabilized liquid/liquid interfaces are an important and growing class of bioinspired materials that combine the structural and functional capabilities of advanced synthetic materials with naturally evolved biophysical systems. These platforms have the potential to serve as selective membranes for chemical separations and molecular sequencers and to even mimic neuromorphic computing elements. Despite the diversity in function, basic insight into the assembly of well-defined amphiphilic polymers to form functional structures remains elusive, which hinders the continued development of these technologies.

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.

Author Correction: Dynamical nonlinear memory capacitance in biomimetic membranes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dynamical nonlinear memory capacitance in biomimetic membranes.

Two-terminal memory elements, or memelements, capable of co-locating signal processing and memory via history-dependent reconfigurability at the nanoscale are vital for next-generation computing materials striving to match the brain's efficiency and flexible cognitive capabilities. While memory resistors, or memristors, have been widely reported, other types of memelements remain underexplored or undiscovered. Here we report the first example of a volatile, voltage-controlled memcapacitor in which capacitive memory arises from reversible and hysteretic geometrical changes in a lipid bilayer that mimics the composition and structure of biomembranes.

Assembly and Characterization of Biomolecular Memristors Consisting of Ion Channel-doped Lipid Membranes.

The ability to recreate synaptic functionalities in synthetic circuit elements is essential for neuromorphic computing systems that seek to emulate the cognitive powers of the brain with comparable efficiency and density. To date, silicon-based three-terminal transistors and two-terminal memristors have been widely used in neuromorphic circuits, in large part due to their ability to co-locate information processing and memory. Yet these devices cannot achieve the interconnectivity and complexity of the brain because they are power-hungry, fail to mimic key synaptic functionalities, and suffer from high noise and high switching voltages.

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.

Memristive Ion Channel-Doped Biomembranes as Synaptic Mimics.

Solid-state neuromorphic systems based on transistors or memristors have yet to achieve the interconnectivity, performance, and energy efficiency of the brain due to excessive noise, undesirable material properties, and nonbiological switching mechanisms. Here we demonstrate that an alamethicin-doped, synthetic biomembrane exhibits memristive behavior, emulates key synaptic functions including paired-pulse facilitation and depression, and enables learning and computing. Unlike state-of-the-art devices, our two-terminal, biomolecular memristor features similar structure (biomembrane), switching mechanism (ion channels), and ionic transport modality as biological synapses while operating at considerably lower power.

Evaporation-induced monolayer compression improves droplet interface bilayer formation using unsaturated lipids.

In this article, we report on a new experimental methodology to enable reliable formation of droplet interface bilayer (DIB) model membranes with two types of unsaturated lipids that have proven difficult for creating stable DIBs. Through the implementation of a simple evaporation technique to condition the spontaneously assembled lipid monolayer around each droplet, we increased the success rates of DIB formation for two distinct unsaturated lipids, namely 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl--glycero-3-phosphocholine (POPC), from less than 10% to near 100%. Separately, using a pendant drop tensiometer, we learned that: (a) DOPC and POPC monolayers do not spontaneously assemble into their tightest possible configurations at an oil-water interface, and (b) reducing the surface area of a water droplet coated with a partially packed monolayer leads to a more tightly packed monolayer with an interfacial tension lower than that achieved by spontaneous assembly alone.

Capacitive Detection of Low-Enthalpy, Higher-Order Phase Transitions in Synthetic and Natural Composition Lipid Membranes.

In-plane lipid organization and phase separation in natural membranes play key roles in regulating many cellular processes. Highly cooperative, first-order phase transitions in model membranes consisting of few lipid components are well understood and readily detectable via calorimetry, densitometry, and fluorescence. However, far less is known about natural membranes containing numerous lipid species and high concentrations of cholesterol, for which thermotropic transitions are undetectable by the above-mentioned techniques.

Hydrodynamic trapping for rapid assembly and in situ electrical characterization of droplet interface bilayer arrays.

The droplet interface bilayer (DIB) is a modular technique for assembling planar lipid membranes between water droplets in oil. The DIB method thus provides a unique capability for developing digital, droplet-based membrane platforms for rapid membrane characterization, drug screening and ion channel recordings. This paper demonstrates a new, low-volume microfluidic system that automates droplet generation, sorting, and sequential trapping in designated locations to enable the rapid assembly of arrays of DIBs.

Reversible, voltage-activated formation of biomimetic membranes between triblock copolymer-coated aqueous droplets in good solvents.

Biomimetic membranes assembled from block copolymers attract considerable interest because they exhibit greater stability and longetivity compared to lipid bilayers, and some enable the reconstitution of functional transmembrane biomolecules. Yet to-date, block copolymer membranes have not been achieved using the droplet interface bilayer (DIB) method, which uniquely allows assembling single- and multi-membrane networks between water droplets in oil. Herein, we investigate the formation of poly(ethylene oxide)-b-poly(dimethyl siloxane)-b-poly(ethylene oxide) triblock copolymer-stabilized interfaces (CSIs) between polymer-coated aqueous droplets in solutions comprising combinations of decane, hexadecane and AR20 silicone oil.

Droplet immobilization within a polymeric organogel improves lipid bilayer durability and portability.

The droplet interface bilayer (DIB) is a promising technique for assembling lipid membrane-based materials and devices using water droplets in oil, but it has largely been limited to laboratory environments due to its liquid construction. With a vision to transform this lab-based technique into a more-durable embodiment, we investigate the use of a polymer-based organogel to encapsulate DIBs within a more-solid material matrix to improve their handling and portability. Specifically, a temperature-sensitive organogel formed from hexadecane and poly[styrene-b-(ethylene-co-butylene)-b-styrene] (SEBS) triblock copolymer is used to replace the liquid solvent that surrounds the lipid-coated droplets to establish a novel liquid-in-gel DIB system.

Toward cell-inspired materials that feel: measurements and modeling of mechanotransduction in droplet-based, multi-membrane arrays.

The droplet interface bilayer (DIB) was recently used to show that a 5 nm thick lipid membrane placed near a vibrating synthetic hair could transduce hair motion into electrical current. Herein, we study for the first time mechanoelectrical transduction of hair motion using multi-membrane DIB arrays formed with more than 2 droplets connected in series, and we introduce a transduction model to investigate how airflow across the hair generates current in a membrane-based hair cell. Measurements of sensing currents across every membrane in serial chains of up to 5 connected droplets demonstrate that perturbation of a single hair creates vibrations that propagate across several droplets, allowing for membranes that are not directly attached to the hair to still transduce its motion.