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

Summary

Soft, low-power, biomolecular memristors leverage similar composition, structure, and switching mechanisms of bio-synapses. Presented here is a protocol to assemble and characterize biomolecular memristors obtained from insulating lipid bilayers formed between water droplets in oil. The incorporation of voltage-activated alamethicin peptides results in memristive ionic conductance across the membrane.

Abstract

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. To overcome these limitations, we have developed and characterized a biomolecular memristor that mimics the composition, structure, and switching characteristics of biological synapses. Here, we describe the process of assembling and characterizing biomolecular memristors consisting of a 5 nm-thick lipid bilayer formed between lipid-functionalized water droplets in oil and doped with voltage-activated alamethicin peptides. While similar assembly protocols have been used to investigate biophysical properties of droplet-supported lipid membranes and membrane-bound ion channels, this article focuses on key modifications of the droplet interface bilayer method essential for achieving consistent memristor performance. Specifically, we describe the liposome preparation process and the incorporation of alamethicin peptides in lipid bilayer membranes, and the appropriate concentrations of each constituent as well as their impact on the overall response of the memristors. We also detail the characterization process of biomolecular memristors, including measurement and analysis of memristive current-voltage relationships obtained via cyclic voltammetry, as well as short-term plasticity and learning in response to step-wise voltage pulse trains.

Introduction

It is widely recognized that biological synapses are responsible for the high efficiency and enormous parallelism of the brain due to their ability to learn and process information in highly adaptive ways. This coordinated functionality emerges from multiple, highly complex molecular mechanisms that drive both short-term and long-term synaptic plasticity^1,2,3,4,5. Neuromorphic computing systems aim to emulate synaptic functionalities at levels approaching the density, complexity, and energy efficiency of th....

Protocol

1. General Instructions and Precautions

1. Select suitable, undamaged measuring/mixing glassware (flasks, beakers, etc.) and other labware (spatulas, scoops, etc.) for use.
2. Handle glassware carefully to avoid damaging, and wear latex or nitrile gloves to avoid contaminating the glassware/labware with residues from fingertips and to protect your skin.
3. Clean chosen glassware/labware thoroughly using detergent solution and water by scrubbing with a soft bottle brush until clean and all residues are removed.
4. Rinse thoroughly with tap water and then with deionized (DI) water. Place on drying rack to air dry.

Results

Figure 1 displays the experimental setup used to assemble and characterize the biomolecular memristor. Lowering the free ends of the electrodes to the bottom of the oil reservoir, as shown in Figure 1b, was found helpful to minimize vibrations of the electrodes and droplets that can result in variations in measured current and bilayer area, especially in cases where heating the oil can generate convective flow in the oil. Figure 2 s.......

Discussion

This paper presents a protocol for assembling and characterizing biomolecular memristors based on ion channel-doped synthetic biomembranes formed between two droplets of water in oil. The soft-matter, two-terminal device is designed and studied to: 1) overcome constraints that are associated with solid-state technology, such as high noise, high energy consumption, and high switching voltages, 2) more closely mimic the composition, structure, switching mechanisms of biological synapses, and 3) explore the mechanisms and f.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
1,2-diphytanoy-sn-glycero-3-phosphocholine (DPhPC)	Avanti Polar Lipids	850356P/850356C	Purchased as lyophilized powder (P) or in chloroform (C)
Agarose	Sigma-Aldrich	A9539
Agarose (0.5g Agarose Tablets)	Benchmark	A2501	You can either use the powder form or the tablets
Alamethicin	AG Scientific	A-1286
Analytical balance	Mettler Toledo	ME204TE/00
Axopatch 200B Amplifier	Molecular Devices	-
BK Precision 4017B 10 MHz DDs Sweep/Function Generator	Digi-Key	BK4017B-ND
Borosilicate Glass Capillaries	World Precision Instruments	1B100F-4
Brain Total Lipid Extracts (Porcine)	Avanti Polar Lipids	131101
DigiData 1440A system	Molecular Devices	-
Extruder Set With Holder/Heating Block	Avanti Polar Lipids	610000	This includes a mini-extruder, 2 syringes, 100 PC membranes, 100 filter supports, and 1 holder/heating block
Freezer (-20 °C)	VWR International	SCUCBI0420AD
Glassware	VWR International	-
Hexadecane, 99%	Sigma-Aldrich	544-76-3
Isopropyl Alcohol	VWR International	BDH1133-4LP
Microelectrode Holder	World Precision Instruments	MEH1S
MOPS	Sigma-Aldrich	M1254
Nitrogen (N2) Gas	Airgas	UN1066
Parafilm M All-Purpose Laboratory Film	Parafilm	PM999
Powder Free Soft Nitrile Examination Gloves	VWR International	CA89-38-272
Precleaned Microscope Sildes	Fisher Scientific	22-267-013
Refrigirator (4 °C)	VWR International	SCUCFS-0504G
Silver wire	GoodFellow	147-346-94	Different diameters could be used depending on the application
Sodium Chloride (KCl)	Sigma-Aldrich	P3911
Stirring Hot Plate	Thermo Scientific	SP131325
VWR Light-Duty Tissue Wipers	VWR International	82003-820
VWR Scientific 50D Ultrasonic Cleaner	VWR International	13089