skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Heterosynaptic plasticity in biomembrane memristors controlled by pH

Journal Article · · MRS Bulletin

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

Research Organization:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH)
Grant/Contract Number:
AC0500OR22725; AC05-00OR22725; R35GM140846
OSTI ID:
1884351
Alternate ID(s):
OSTI ID: 1897002
Journal Information:
MRS Bulletin, Journal Name: MRS Bulletin Vol. 48 Journal Issue: 1; ISSN 0883-7694
Publisher:
Cambridge University Press (CUP)Copyright Statement
Country of Publication:
United States
Language:
English

References (31)

Neuromorphic computing for temporal scientific data classification conference July 2017
Direct in situ measurement of specific capacitance, monolayer tension, and bilayer tension in a droplet interface bilayer journal January 2015
Biomimetic, Soft-Material Synapse for Neuromorphic Computing: from Device to Network conference November 2018
Functional consequences of lipid packing stress journal July 2000
Antimicrobial peptides of multicellular organisms journal January 2002
The influence of membrane lateral pressures on simple geometric models of protein conformational equilibria journal August 1999
Statistical analysis of alamethicin channels in black lipid membranes journal December 1974
Feeling the hidden mechanical forces in lipid bilayer is an original sense journal May 2014
Is Heterosynaptic modulation essential for stabilizing hebbian plasiticity and memory journal October 2000
Vesicle and bilayer formation of diphytanoylphosphatidylcholine (DPhPC) and diphytanoylphosphatidylethanolamine (DPhPE) mixtures and their bilayers’ electrical stability journal February 2011
Probability of alamethicin conductance states varies with nonlamellar tendency of bilayer phospholipids journal July 1993
Heating-Enabled Formation of Droplet Interface Bilayers Using Escherichia coli Total Lipid Extract journal December 2014
The nature of the voltage-dependent conductance induced by alamethicin in black lipid membranes journal December 1973
Protonation‐Driven Membrane Insertion of a pH‐Low Insertion Peptide journal August 2016
Effect of pH on the Interfacial Tension of Lipid Bilayer Membrane journal February 2000
A novel pH-dependent membrane peptide that binds to EphA2 and inhibits cell migration journal September 2018
Global modulatory heterosynaptic mechanisms in bio-polymer electrolyte gated oxide neuron transistors journal August 2020
If it’s pinched it’s a memristor journal September 2014
Alamethicin. A rich model for channel behavior journal January 1984
Macromolecular Crowding Affects Voltage-Dependent Alamethicin Pore Formation in Lipid Bilayer Membranes journal May 2020
Ion Channels of Alamethicin Dimer N-Terminally Linked by Disulfide Bond journal July 2003
Networks of spiking neurons: The third generation of neural network models journal December 1997
Action of Antimicrobial Peptides:  Two-State Model journal July 2000
Memristive Ion Channel-Doped Biomembranes as Synaptic Mimics journal March 2018
Memristive Physically Evolving Networks Enabling the Emulation of Heterosynaptic Plasticity journal October 2015
Lipid packing stress and polypeptide aggregation: alamethicin channel probed by proton titration of lipid charge journal January 1999
The Negative Charge of the Membrane Has Opposite Effects on the Membrane Entry and Exit of pH-Low Insertion Peptide journal February 2015
Solution pH Alters Mechanical and Electrical Properties of Phosphatidylcholine Membranes: Relation between Interfacial Electrostatics, Intramembrane Potential, and Bending Elasticity journal April 2007
pH modulation of transport properties of alamethicin oligomers inserted in zwitterionic-based artificial lipid membranes journal November 2007
Determination of the Membrane Translocation pK of the pH-Low Insertion Peptide journal August 2017
Hydrophobic mismatch between proteins and lipids in membranes journal November 1998

Similar Records

Assembly and Characterization of Biomolecular Memristors Consisting of Ion Channel-doped Lipid Membranes
Journal Article · Tue Jan 01 00:00:00 EST 2019 · Journal of Visualized Experiments · OSTI ID:1884351

Memristive Ion Channel-Doped Biomembranes as Synaptic Mimics
Journal Article · Mon Mar 26 00:00:00 EDT 2018 · ACS Nano · OSTI ID:1884351

Macromolecular Crowding Affects Voltage-Dependent Alamethicin Pore Formation in Lipid Bilayer Membranes
Journal Article · Tue May 19 00:00:00 EDT 2020 · Journal of Physical Chemistry. B, Condensed Matter, Materials, Surfaces, Interfaces and Biophysical Chemistry · OSTI ID:1884351