Characterizing the Structure and Interactions of Model Lipid Membranes Using Electrophysiology

Abstract

The cell membrane is a protective barrier whose configuration determines the exchange both between intracellular and extracellular regions and within the cell itself. Consequently, characterizing membrane properties and interactions is essential for advancements in topics such as limiting nanoparticle cytotoxicity. Characterization is often accomplished by recreating model membranes that approximate the structure of cellular membranes in a controlled environment, formed using self-assembly principles. The selected method for membrane creation influences the properties of the membrane assembly, including their response to electric fields used for characterizing transmembrane exchanges. When these self-assembled model membranes are combined with electrophysiology, it is possible to exploit their non-physiological mechanics to enable additional measurements of membrane interactions and phenomena. This review describes several common model membranes including liposomes, pore-spanning membranes, solid supported membranes, and emulsion-based membranes, emphasizing their varying structure due to the selected mode of production. Next, electrophysiology techniques that exploit these structures are discussed, including conductance measurements, electrowetting and electrocompression analysis, and electroimpedance spectroscopy. The focus of this review is linking each membrane assembly technique to the properties of the resulting membrane, discussing how these properties enable alternative electrophysiological approaches to measuring membrane characteristics and interactions.

Studying the Mechanics of Membrane Permeabilization through Mechanoelectricity

“…Membrane disruption mechanics are often studied in a controlled environment through the formation of model lipid membranes. These lipid membranes mimic the fundamental structure of biological membranes and contain a double layer of phospholipids, produced in vitro through a variety of methods . Model membranes present a simplified yet tunable architecture, providing a repeatable and adjustable platform for investigating membrane interactions through various approaches. − For example, super-resolution microscopy allows for the characterization of lipid domains, interferometry has been utilized to observe real-time binding of proteins to liposomes, and X-ray and neutron techniques allow for the characterization of functional nanoparticles with planar supported model membranes .…”

“…Herein, we propose a new technique for tracking membrane–agent interactions prior to permeabilization, based on membrane electrophysiology. Electrophysiology relies on monitoring changes in the bilayer’s electrical properties, ,− where the membrane is approximated as a capacitor and a resistor in parallel, ,, as illustrated in Figure . The membrane capacitance arises due to the difference in hydrophilic–hydrophobic permittivity of the lipid regions, , whereas its resistance is a result of its well-packed hydrophobic interior.…”

Disentangling Memristive and Memcapacitive Effects in Droplet Interface Bilayers Using Dynamic Impedance Spectroscopy

“…[ 18 ] Explicitly probing the response of multiple sinusoidal frequencies allows for analysis in frequency‐space, enabling deconvolution of electrical elements like capacitors and resistors. [ 16–18,21 ] Here, we utilize dEIS to disentangle the system's memristive and memcapacitive properties arising from molecular and conformational changes in the lipid bilayer. By separating these processes, we provide: (1) new insights into the design of new neuromorphic devices; (2) an understanding as to how to build multiple memelement functionalities into a single two‐terminal device; (3) demonstration of memristive behavior from dielectric loss change and not solely ion transport through the bilayer; and (4) a proof‐of‐principle demonstration for the use of dEIS in evaluating the next‐generation of biomimetic electronic devices.…”

Silicon Nitride-Based Micro-Apertures Coated with Parylene for the Investigation of Pore Proteins Fused in Free-Standing Lipid Bilayers

“…Bacterial survival largely depends on the cell-to-cell communication through OMVs [ 16 , 17 , 18 , 19 , 20 ]. Unlike patch clamping, lipid bilayer membranes (BLM) free standing in a hydrophobic aperture are very suitable to electrically investigate OMV-BLM interactions [ 21 ]. A main advantage is that both sides of the spanned lipid bilayer are accessible [ 22 ].…”