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

Najem, Joseph S.; Taylor, Graham J.; Armendarez, Nick; Weiss, Ryan; Hasan, Sakib; Rose, Garrett S.; Schuman, Catherine D.; Belianinov, Alex; Sarles, Stephen A.; Collier, C. Patrick

doi:10.3791/58998

Cited by 7 publications

(11 citation statements)

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“…The values of the fitted parameters in Table I are consistent with models that focus on how surface charge affects pore formation in AMPs like alamethicin 15 -charge plays a major role in how biological membranes interact with molecules. For example, it has been shown that changes in the surface potential and surface charge density by proton titration of the ionizable groups in charged PS lipids result in changes to the elastic properties of the bilayer.…”

Section: Discussionsupporting

confidence: 79%

“…For example, it has been shown that changes in the surface potential and surface charge density by proton titration of the ionizable groups in charged PS lipids result in changes to the elastic properties of the bilayer. 15,16 In the case of alamethicin-DPhPC bilayers, two titrations of exchangeable hydrogens can occur as a function of pH, namely, titration of the membrane surface charge, and titration of the alamethicin channel conductance.…”

Section: Discussionmentioning

confidence: 99%

“…The sharp increase in pore activity that we observed at pH 4.97 on the other hand is consistent with reports of enhanced probability for alamethicin pore formation in more acidic environments. 15 Although increased acidity enhanced the probability of a pore being in a higher conductance state, the channel conductance itself was largely unaffected. 15 This is an important observation because it shows that the enhanced currents at lower pH are due mainly to increases in the number of active channels in the membrane, and not intrinsic pore conductance.…”

Section: Discussionmentioning

confidence: 99%

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Heterosynaptic plasticity in biomembrane memristors controlled by pH

et al. 2022

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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

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Heterosynaptic plasticity in biomembrane memristors controlled by pH

et al. 2022

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“…Positive current represents flow of positive ions from the cis side of the bilayer to the trans side (ground). All two-terminal MzBS systems were assembled and characterized as described in the Exerimental Section and elsewhere. , In this work, we added Mz to both droplets such that Mz was available on both faces of the bilayer and could form ion channels at both positive and negative cis potentials. This choice resulted in symmetric current–voltage ( i–v ) relationships, such as those shown in Figure c and Figure S3 for an MzBS lipid bilayer formed with a 1:1 mol ratio of 1,2-dioleoyl- sn -glycero-3-phosphocholine (DOPC) and 1,2-diphytanoyl- sn -glycero-3-phosphocholine (DPhPC) lipids.…”

Section: Resultsmentioning

confidence: 99%

Short-Term Facilitation-Then-Depression Enables Adaptive Processing of Sensory Inputs by Ion Channels in Biomolecular Synapses

Maraj

Najem

Weiss

et al. 2021

ACS Appl. Electron. Mater.

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Providing AI platforms with perceptual capabilities at low energy cost is imperative to making them more human-like. This goal is contingent on developing stimuliresponsive materials that closely emulate diverse synaptic functions needed to enhance machine learning applications. Here a biomolecular device is reported, consisting of an insulating lipid membrane doped with voltage-activated, ion channel-forming monazomycin (Mz) species, that display diode-like current−voltage characteristics and emulate short-term facilitation-then-depression on time scales relevant to habituation in human sensory systems. Subjected to a slow train of voltage pulses, devices show only facilitation upon Mz channel formation. At higher pulse rates, faster facilitation creates later depression upon Mz inactivation. The device is integrated as a biomolecular synapse in an organic−inorganic hybrid afferent model to demonstrate its ability to process sensory inputs and mimic bidirectional retinal adaptation and sensitization. These findings highlight the value of instilling complex synaptic plasticity into engineered systems, which is useful for adaptive neuroprosthetics and biosignal processing.

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“…Concurrently, metabolic engineers have leveraged these and other compartments to cluster exogenous enzymes to produce novel products 11 , 12 . Cellular engineers interested in programming cellular behaviors and decision-making embed new molecules into cells that function as receptors or switches, to augment or redirect native behaviors 39 – 44 . Here, we expand the toolkit for cellular engineering by constructing a designer membraneless organelle system from disordered proteins that is capable of efficiently client sequestration and release.…”

Section: Discussionmentioning

confidence: 99%

Designer membraneless organelles sequester native factors for control of cell behavior

et al. 2021

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Subcellular compartmentalization of macromolecules increases flux and prevents inhibitory interactions to control biochemical reactions. Inspired by this functionality, we sought to build designer compartments that function as hubs to regulate the flow of information through cellular control systems. We report a synthetic membraneless organelle platform to control endogenous cellular activities through sequestration and insulation of native proteins. We engineer and express a disordered protein scaffold to assemble micron size condensates and recruit endogenous clients via genomic tagging with high-affinity dimerization motifs. By relocalizing up to ninety percent of a targeted enzymes to synthetic condensates, we efficiently control cellular behaviors, including proliferation, division, and cytoskeletal organization. Further, we demonstrate multiple strategies for controlled cargo release from condensates to switch cells between functional states. These synthetic organelles offer a powerful and generalizable approach to modularly control cell decision-making in a variety of model systems with broad applications for cellular engineering.

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

Cited by 7 publications

References 0 publications

Heterosynaptic plasticity in biomembrane memristors controlled by pH

Heterosynaptic plasticity in biomembrane memristors controlled by pH

Short-Term Facilitation-Then-Depression Enables Adaptive Processing of Sensory Inputs by Ion Channels in Biomolecular Synapses

Designer membraneless organelles sequester native factors for control of cell behavior

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