Charles Patrick Collier

Droplet interface bilayers (DIBs) offer a tunable platform for probing the electromechanical properties of lipid and lipid-peptide membranes under controlled electrical stimulation. DIBs enable both single-channel and ensemble ion conductance measurements over membrane areas orders of magnitude larger than those accessible by traditional patch clamp techniques, thereby allowing membrane-level analyses of electromechanical deformation and its influence on ion-conducting peptides. By systematically tuning membrane structure through the bulk hydrocarbon oil phase (e.g., hexadecane [C16] vs. dodecane/hexadecane [C12/C16] [25%/75%, v/v]), this bottom-up platform enables systematic variation of membrane composition and oil environment, which influence membrane viscoelasticity and structural reorganization, and thereby peptide ion conduction. Detailed procedures are provided for the assembly of gramicidin A-doped 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC) membranes using different hydrocarbon oil compositions and for the application of voltage-pulse protocols that drive membranes into metastable electromechanical states. Adaptive membrane ion conduction is characterized, including short-term plasticity-like (STP-like) and long-term potentiation- and depression-like (LTP-like/LTD-like) responses in a model membrane system. More broadly, this protocol provides a robust, reproducible approach for systematically investigating composition-dependent, membrane-level electromechanical contributions to synaptic-like conductive behavior and for understanding how lipid membrane environments modulate ion channel function.

A rotaxane consisting of a macrocycle ring with two azobenzene units mechanically interlocked onto a bolaamphiphilic axle was incorporated into droplet interface bilayers (DIBs). The azobenzene groups on the ring underwent quasi‐reversible, photoisomerization‐induced cycling between 1‐ E and 1 ‐ Z configurations when irradiated with 370 and 467 nm light, respectively, enabling programmable access to different history‐dependent electrical behaviors from the same membrane. In the 1 ‐E configuration, bilayers exhibited type‐IIactive memristance that coincided with increasingly elevated ionic conduction, associated with progressively enhanced bilayer permeability during voltage cycling. In the 1 ‐Z configuration, bilayers displayed type‐I, passive memcapacitive behavior, reflecting tighter lipid packing and reduced ionic permeability. Photoswitching also yielded a nonvolatile, photoresponsive memcapacitor that could be modulated repetitively with negligible loss, likely via reversible changes in membrane thickness. Concurrent ohmic leakage currents across the membrane were less than 0.3%. These results agree with previous studies with increasing membrane permeability using photoswitchable rotaxanes and provide new insights into the coupling between volatile and nonvolatile memcapacitance during photoisomerization. More broadly, they demonstrate a new strategy for the manipulation of neuromorphic behaviors in soft materials using light, with implications for brain‐inspired computation and sensing.

Melatonin, a hormone primarily produced by the brain's pineal gland, not only regulates circadian rhythms, but also influences the structural and biophysical properties of neuronal membranes. Its amphiphilic nature enables direct incorporation into lipid bilayers and preferential interactions with cholesterol-rich lipid rafts, critical hubs for cellular signaling and membrane organization. Despite increasing recognition of its membrane activity, the molecular basis of melatonin's interactions with coexisting liquid-ordered (L_o) and liquid-disordered (L_d) phases remains unclear. Here, we combine small-angle neutron scattering (SANS) and all-atom molecular dynamics simulations to examine model neuronal membranes composed of DSPC, DOPC, POPC, and cholesterol. Our results show that melatonin preserves domain morphology while adopting distinct orientations within the bilayer and at the membrane interface, allowing both lateral and transmembrane bridging across lipid phases. These findings establish the molecular underpinnings of melatonin's modulation of membrane heterogeneity and provide strong support for its receptor-independent actions.

Despite their adaptability and mechanical stability, Pickering emulsions based on the interfacial assembly of colloidal particles have not found use in iontronics, since the dense interfacial packing of micron-sized particles precludes functional connectivity between two droplets. Here, we introduce a chemically reconfigurable droplet interface bilayer (DIB) platform based on the interfacial assembly of nanoparticle-surfactants (NPSs) that enables spontaneous or field-induced formation of ion-conducting nanochannels, eliminating the need of ionophores or nanochannel-forming proteins. These nanoscopic channels emerge from packing defects in the jammed interfacial assemblies of the charged NPSs and support size and charge selective, hysteretic ion transport governed by interfacial electrostatics and dimensional constraints. The NPS-DIBs show short-term and long-term plasticity, hallmarks of neuromorphic behavior, that are mediated by the structural and chemical design of the bilayer. These assemblies establish a versatile, chemically tunable platform that couples soft-matter mechanics with interfacial ionic functionality, offering a robust foundation for soft iontronic systems.

Human neural networks of interconnected neurons have evolved to be remarkably efficient and are capable of learning and memory through the brain’s synaptic plasticity, including short-term plasticity (STP), and long-term potentiation (LTP) and depression (LTD). These activity-dependent mechanisms induce changes in synaptic efficiency over both transient and extended timescales. Understanding the molecular basis of learning and memory is central to deciphering brain function and advancing therapeutics for neurodegenerative diseases. Here, we report that lipid bilayers with embedded gramicidin A ion channels can structurally reorganize when interrogated using a neurologically inspired electrical stimulation protocol, adopting metastable structures with enhanced STP response and emergent LTP or LTD. Specifically, voltage-induced electrocompression is found to restructure membranes, driving them into nonequilibrium steady states with enhanced stability and increased ionic conductivity, leading to stronger and persistent membrane ion conductance. These results show how membrane restructuring and emergent complexity may regulate synaptic plasticity at the molecular level.

Amphiphilic charged oligomers (oligodimethylsiloxane – methylimidazolium cation, ODMS‐MIM ⁽⁺⁾), assemble into bilayers using the droplet interface bilayer (DIB) platform, possess similar size and functionality as phospholipid bilayers, but exhibit increased stability. The oligomer ionic headgroups (MIM⁽⁺⁾) are covalently bound to monodisperse, short‐chain (n = 13) hydrophobic tails (ODMS). These self‐assemble as monolayer brushes at the oil–aqueous interface of water droplets that are influenced by both the charged cationic headgroups, and the nature of the covalently attached tails in the organic phase. Charge regulation (CR) stabilizes the formation of ordered, molecularly close‐packed brush phases, which results in highly insulating, stable DIB membranes, with contributions from specific ion‐pairing effects, Debye screening, and voltage‐dependent electrocompressive stresses. In the oil phase, interactions between hexadecane, a good solvent for ODMS, and the hydrophobic tails result in extended waiting times for bilayer formation compared to phospholipid DIBs, for which hexadecane is a poor solvent. Close agreement between experimental values and predictions for two key parameters, the critical membrane thickness, h_c, and maximal grafted headgroup density, Γ₀, validate an electrostatic CR model consisting of adsorption and partial neutralization of counterions at a charged interface.

We demonstrate, using non-equilibrium molecular dynamics simulations, that lipid membrane capacitance varies with surface charge accumulation linked to membrane shape and curvature changes. Specifically, we show that lipid membranes exhibit a hysteretic response when exposed to oscillatory electric fields. The electromechanical coupling in these membranes leads to hysteretic buckling, in which the membrane can spontaneously buckle in one of two distinct directions along the electric field, even for the same ionic charge accumulation at the water-membrane interface. In this regard, these binary buckled membrane states suggest potential applications in neuromorphic computing. Their bistable nature, characterized by two distinct and stable configurations, could serve as a foundation for implementing memory storage systems and logic operations. Furthermore, we introduce a circuit model that captures these dynamic effects, offering insights into emergent memory effects in electrically stimulated lipid membranes. Finally, this work presents lipid bilayers as dynamic, adaptable elements and suggests a new platform for exploring energy storage, information processing, and memory encoding at the lipid membrane level.

Biological memory is the ability to develop, retain, and retrieve information over time. Currently, it is widely accepted that memories are stored in synapses (i.e., connections between brain cells throughout the brain) through a process known as synaptic plasticity, which leads to either long-term potentiation (LTP) or long-term depression (LTD). However, the strengthening (LTP) and weakening (LTD) of synapses involve post-translational modifications to neural networks requiring de novo gene expression, a lengthy and energetically expensive process. Recently, we observed that lipid bilayers in the absence of peptides/proteins are capable of LTP, not unlike what has been observed in mammals and birds. As such, this finding has prompted us to postulate that the lipid bilayer provides a good model for understanding the molecular basis of biological memory. In this article, we discuss the status, challenges, and opportunities of neuronal plasma membranes as structures for biological memory and learning, therapeutic targets for various brain disorders, and platforms for neural network developments.