Phospholipid bilayers can be described as capacitors whose capacitance per unit area (specific capacitance, Cm) is determined by their thickness and dielectric constant–independent of applied voltage. It is also widely assumed that the Cm of membranes can be treated as a “biological constant”. Recently, using droplet interface bilayers (DIBs), it was shown that zwitterionic phosphatidylcholine (PC) lipid bilayers can act as voltage-dependent, nonlinear memory capacitors, or memcapacitors. When exposed to an electrical “training” stimulation protocol, capacitive energy storage in lipid membranes was enhanced in the form of long-term potentiation (LTP), which enables biological learning and long-term memory. LTP was the result of membrane restructuring and the progressive asymmetric distribution of ions across the lipid bilayer during training, which is analogous, for example, to exponential capacitive energy harvesting from self-powered nanogenerators. Here, we describe how LTP could be produced from a membrane that is continuously pumped into a nonequilibrium steady state, altering its dielectric properties. During this time, the membrane undergoes static and dynamic changes that are fed back to the system’s potential energy, ultimately resulting in a membrane whose modified molecular structure supports long-term memory storage and LTP. Here, we also show that LTP is very sensitive to different salts (KCl, NaCl, LiCl, and TmCl3), with LiCl and TmCl3 having the most profound effect in depressing LTP, relative to KCl. This effect is related to how the different cations interact with the bilayer zwitterionic PC lipid headgroups primarily through electric-field-induced changes to the statistically averaged orientations of water dipoles at the bilayer headgroup interface.
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Rapid and Real-Time Measurement of Membrane Potential Through Intramembrane Field Compensation
Synthetic lipid membranes are self-assembled biomolecular double layers designed to approximate the properties of living cell membranes. These membranes are employed as model systems for studying the interactions of cellular envelopes with the surrounding environment in a controlled platform. They are constructed by dispersing amphiphilic lipids into a combination of immiscible fluids enabling the biomolecules to self-assemble into ordered sheets, or monolayers at the oil-water interface. The adhesion of two opposing monolayer sheets forms the membrane, or the double layer. The mechanical properties of these synthetic membranes often differ from biological ones mainly due to the presence of residual solvent in between the leaflets. In fact, the double layer compresses in response to externally applied electrical field with an intensity that varies depending on the solvent present. While typically viewed as a drawback associated with their assembly, in this work the elasticity of the double layer is utilized to further quantify complex biophysical phenomena. The adsorption of charged molecules on the surface of a lipid bilayer is a key property to decipher biomolecule interactions at the interface of the cell membrane, as well as to develop effective antimicrobial peptides and similar membrane-active molecules. This adsorption generates a difference in the boundary potentials on either side of the membrane which may be tracked through electrophysiology. The soft synthetic membranes produced in the laboratory compress when exposed to an electric field. Tracking the minimum membrane capacitance allows for quantifying when the intrinsic electric field produced by the asymmetry is properly compensated by the supplied transmembrane voltage. The technique adopted in this work is the intramembrane field compensation (IFC). This technique focuses on the current generated by the bilayer in response to a sinusoidal voltage with a DC component, VDC. Briefly, the output sinusoidal current is divided into its harmonics and the second harmonic equals zero when VDC compensates the internal electric field. In this work, we apply the IFC technique to droplet interface bilayers (DIB) enabling the development of a biological sensor. A certain membrane elasticity is needed for accurate measurements and is tuned through the solvent selection. The asymmetric DIBs are formed, and an automated PID-controlled IFC design is implemented to rapidly track and compensate the membrane asymmetry. The closed loop system continuously reads the current and generates the corresponding voltage until the second harmonic is abated. This research describes the development and optimization of a biological sensor and examines how varying the structure of the synthetic membrane influences its capabilities for detecting membrane-environment interactions. This platform may be applied towards studying the interactions of membrane-active molecules and developing models for the associated phenomena to enhance their design.
more » « less- Award ID(s):
- 1903965
- PAR ID:
- 10286876
- Date Published:
- Journal Name:
- Smart Materials, Adaptive Structures, and Intelligent Systems 2020
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Biological supramolecular assemblies, such as phospholipid bilayer membranes, have been used to demonstrate signal processing via short-term synaptic plasticity (STP) in the form of paired pulse facilitation and depression, emulating the brain’s efficiency and flexible cognitive capabilities. However, STP memory in lipid bilayers is volatile and cannot be stored or accessed over relevant periods of time, a key requirement for learning. Using droplet interface bilayers (DIBs) composed of lipids, water and hexadecane, and an electrical stimulation training protocol featuring repetitive sinusoidal voltage cycling, we show that DIBs displaying memcapacitive properties can also exhibit persistent synaptic plasticity in the form of long-term potentiation (LTP) associated with capacitive energy storage in the phospholipid bilayer. The time scales for the physical changes associated with the LTP range between minutes and hours, and are substantially longer than previous STP studies, where stored energy dissipated after only a few seconds. STP behavior is the result of reversible changes in bilayer area and thickness. On the other hand, LTP is the result of additional molecular and structural changes to the zwitterionic lipid headgroups and the dielectric properties of the lipid bilayer that result from the buildup of an increasingly asymmetric charge distribution at the bilayer interfaces.more » « less
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Conference Paper:
- https://doi.org/10.1115/SMASIS2020-2352
