Search for: All records

Abstract In biology, heterosynaptic plasticity maintains homeostasis in synaptic inputs during associative learning and memory, and initiates long-term changes in synaptic strengths that nonspecifically modulate different synapse types. In bioinspired neuromorphic circuits, heterosynaptic plasticity may be used to extend the functionality of two-terminal, biomimetic memristors. In this article, we explore how changes in the pH of droplet interface bilayer aqueous solutions modulate the memristive responses of a lipid bilayer membrane in the pH range 4.97–7.40. Surprisingly, we did not find conclusive evidence for pH-dependent shifts in the voltage thresholds ( V* ) needed for alamethicin ion channel formation in the membrane. However, we did observe a clear modulation in the dynamics of pore formation with pH in time-dependent, pulsed voltage experiments. Moreover, at the same voltage, lowering the pH resulted in higher steady-state currents because of increased numbers of conductive peptide ion channels in the membrane. This was due to increased partitioning of alamethicin monomers into the membrane at pH 4.97, which is below the pKa (~5.3–5.7) of carboxylate groups on the glutamate residues of the peptide, making the monomers more hydrophobic. Neutralization of the negative charges on these residues, under acidic conditions, increased the concentration of peptide monomers in the membrane, shifting the equilibrium concentrations of peptide aggregate assemblies in the membrane to favor greater numbers of larger, increasingly more conductive pores. It also increased the relaxation time constants for pore formation and decay, and enhanced short-term facilitation and depression of the switching characteristics of the device. Modulating these thresholds globally and independently of alamethicin concentration and applied voltage will enable the assembly of neuromorphic computational circuitry with enhanced functionality. Impact statement We describe how to use pH as a modulatory “interneuron” that changes the voltage-dependent memristance of alamethicin ion channels in lipid bilayers by changing the structure and dynamical properties of the bilayer. Having the ability to independently control the threshold levels for pore conduction from voltage or ion channel concentration enables additional levels of programmability in a neuromorphic system. In this article, we note that barriers to conduction from membrane-bound ion channels can be lowered by reducing solution pH, resulting in higher currents, and enhanced short-term learning behavior in the form of paired-pulse facilitation. Tuning threshold values with environmental variables, such as pH, provide additional training and learning algorithms that can be used to elicit complex functionality within spiking neural networks. Graphical abstract 

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. 

It is well known that the lipid distribution in the bilayer leaflets of mammalian plasma membranes (PMs) is not symmetric. Despite this, model membrane studies have largely relied on chemically symmetric model membranes for the study of lipid–lipid and lipid–protein interactions. This is primarily due to the difficulty in preparing stable, asymmetric model membranes that are amenable to biophysical studies. However, in the last 20 years, efforts have been made in producing more biologically faithful model membranes. Here, we review several recently developed experimental and computational techniques for the robust generation of asymmetric model membranes and highlight a new and particularly promising technique to study membrane asymmetry.