About

Lior Sepunaru is an Associate Professor in the Department of Chemistry & Biochemistry at the University of California, Santa Barbara. His research focuses on bioelectronics at the nano scale, including the study of enzyme catalysis and the development of a new generation of biosensors. He completed his Ph.D. at the Weizmann Institute of Science in 2014, working on solid state bioelectronics under the supervision of Prof. David Cahen and Prof. Mordechai Sheves. Following his doctoral studies, he conducted post-doctoral research as a Marie Curie research fellow at the University of Oxford, where he worked on bio-nanoelectrochemistry under the tutelage of Prof. Richard G. Compton.

Research topics

• Biology
• Nanotechnology
• Molecular biology
• Chemistry
• Materials science

Selected publications

• Electric Double Layer Phenomena Near Surfaces Irreversibly Trigger Assembly of Tau Protein

  Journal of the American Chemical Society · 2026-04-01

  articleOpen access

  The reversible folding and assembly of the human brain protein tau are regulated by charge neutralization through limited and reversible phosphorylation, enabling tau to bind tubulin and maintain the structural integrity of neuronal microtubules. However, in neurodegenerative diseases like Alzheimer’s and related tauopathies, tau becomes hyperphosphorylated, detaches from tubulin, and irreversibly assembles into β-structured amyloid filaments responsible for neuronal death. In previous work, we showed that charge neutralization via Faradaic electroreduction of cationic residues in tau and other intrinsically disordered proteins can mimic phosphorylation to trigger protein condensation, folding, and assembly. Here, we demonstrate that even non-Faradaic effects─including large electric fields and concentration gradients in the electric double layer, together with spatial ordering of ions at the solution–electrode interface─can induce folding and assembly of tau, its microtubule-binding region K18, and a 19-residue tau peptide (jR2R3 P301L) containing a mutation known to induce early aggregation in vitro and in vivo. Assembly occurs on different electrode materials at identical effective electric fields, demonstrating independence from the electrode hydrophobicity and electronic structure. Surface-enhanced infrared absorption and plasmon resonance spectroscopies show that near-surface electric fields of ∼1 MV/cm trigger K18 folding and assembly. Ion ordering and charge screening near electrodes at higher salt concentrations (50 vs 1 mM) also reduce Coulombic repulsion between protein monomers and their cationic residues, promoting folding and assembly. Overall, these results show that interfacial electric fields and other non-Faradaic processes can reveal and drive protein misfolding and aggregation, hallmarks of tauopathies and prion-related neurodegenerative diseases.

  PublisherDOI

• Direct measurement of electrocatalyst activity through maximum noise

  Joule · 2026-03-01

  articleSenior author
  PublisherDOI

• Does Turnover Number Represent a Single Value or a Distribution?

  Research Square · 2025-07-17

  preprintOpen access1st authorCorresponding
  PublisherOA PDFDOI

• Sensation of electric fields in the Drosophila melanogaster larva

  Current Biology · 2025-04-01 · 3 citations

  articleOpen access

  Electrosensation has emerged as a crucial sensory modality for social communication, foraging, and predation across the animal kingdom. However, its presence and functional role as well as the neural basis of electric field perception in Drosophila and other invertebrates remain unclear. In environments with controlled electric fields, we identified electrosensation as a new sense in the Drosophila melanogaster larva. We found that the Drosophila larva performs robust electrotaxis: when exposed to a uniform electric field, larvae migrate toward the cathode (negatively charged elecrode) and quickly respond to changes in the orientation of the field to maintain cathodal movement. Through a behavioral screen, we identified a subset of sensory neurons located at the tip of the larval head that are necessary for electrotaxis. Calcium imaging revealed that a pair of Gr66a -positive sensory neurons (one on each side of the head) encodes the strength and orientation of the electric field. Our results indicate that electric fields elicit robust behavioral and neural responses in the Drosophila larva, providing new evidence for the significance of electrosensation in invertebrates. • Drosophila larvae sense electric fields and navigate toward the cathode • Larvae use active sampling with lateral head movements to orient in electric fields • Gr66a -positive and Gr33a -positive sensory neurons are essential for electrotaxis • A Gr66a -positive neuron in the larval head encodes electric field orientation Tadres et al. show that Drosophila larvae detect electric fields, moving toward the cathode via electrotaxis. Gr66a neurons encode field orientation, revealing a new larval sensory ability and expanding our understanding of invertebrate electroreception.

  PublisherDOI

• Electrochemically Driven Optical Dynamics of Reflectin Protein Films

  Advanced Materials · 2025-02-17 · 4 citations

  articleOpen access

  Neuronally triggered phosphorylation drives the dynamic condensation of reflectin proteins, enabling squid to fine tune the colors reflected from specialized skin cells (iridocytes) for camouflage and communication. Reflectin, the primary component of iridocyte lamellae, forms alternating layers of protein and low refractive index extracellular space within membrane-encapsulated structures, acting as a biologically tunable distributed Bragg reflector. In vivo, reflectin condensation induces osmotic dehydration of these lamellae, reducing their thickness and shifting the wavelength of reflected light. Inspired by this natural mechanism, we demonstrate that electrochemical reduction of imidazolium moieties within the protein provides a reversible and tunable method to control the water volume fraction in reflectin thin films, allowing precise, dynamic modulation of the film's refractive index and thickness - mimicking the squid's dynamic color adaptation. To unravel the underlying mechanisms, we developed electrochemical correlative ellipsometry and surface plasmon resonance spectroscopy, enabling real-time analysis of optical property changes of reflectin films. This electrochemically driven approach offers unprecedented control over reflectin condensation dynamics. Our findings not only deepen the understanding of biophysical processes governing cephalopod coloration but also pave the way for bio-inspired materials and devices that seamlessly integrate biological principles with synthetic systems to bridge the biotic-abiotic gap.

  PublisherOA PDFDOI

• Challenges and Opportunities of Intermediate-Temperature (100–350 °C) Electrocatalysis

  ACS electrochemistry. · 2025-12-08

  articleSenior authorCorresponding

  Transitioning to a more sustainable chemical industry requires reevaluating how commodity chemicals are produced. While most industrial transformations currently rely on high temperatures and stoichiometric chemical reductants and oxidants to drive the reactivity, electrification of chemical synthesis presents a promising alternative. With the growing availability of low-cost renewable electricity and continued advances in understanding electrochemical interfaces, electrochemical pathways are increasingly positioned to replace or even surpass the performance of traditional thermochemical routes. In this perspective, we explore the potential for using intermediate temperatures (100–350 °C) to enable enhanced control over reaction thermodynamics relative to conventional thermocatalysis. Particular attention is given to the interplay between entropic contributions within the electrochemical double layer and temperature-dependent reaction kinetics. By examining fundamental relationships governing temperature effects on both thermochemical and electrochemical rate processes, we propose guiding principles for identifying regimes in which intermediate-temperature electrochemical systems can viably displace thermochemical counterparts. We further highlight opportunities for ambient- or near-ambient-pressure electrocatalysis within this temperature window using water and conventional organic solvents, such that mechanistic insights and design strategies established at room temperature may remain applicable. Finally, we conclude by discussing critical challenges and future research priorities for advancing the electrochemical reactor design at intermediate temperatures.

  PublisherDOI

• Electrochemical Investigation of Enzyme Kinetics with an Unmediated, Unmodified Platinum Microelectrode: The Case of Glucose Oxidase

  ACS electrochemistry. · 2025-07-09 · 2 citations

  articleOpen accessSenior authorCorresponding

  We present a simple analytical method for studying the physical parameters governing redox-active enzyme kinetics using microscale electrodes. With the enzyme freely diffusing in solution, the interaction with its natural substrates produces a linearly increasing current corresponding to the reaction rate and the intrinsic thermodynamic properties of the enzyme. We show that external complications, such as artificial mediators or enzyme surface immobilization, can be avoided by using an unmediated, unmodified platinum microelectrode and that control over the dominating kinetic process can be readily achieved by changing the enzyme and (co)substrate concentrations. This is achieved using the glucose oxidase (GOx)/glucose system to compare with standard practice UV-Vis techniques, including the pH dependence of the enzyme activity. We illustrate how this straightforward chronoamperometric measurement is influenced by changes to reaction conditions commonly employed in enzyme investigations, including enzyme and oxygen concentrations as well as pH and the presence of chloride. Our method emphasizes that interpreting a simple increasing slope to analyze enzyme behavior requires ensuring adherence to initial rate assumptions, empirical observation of the current-concentration relationship, and insight from using the ping-pong framework. This enables a discussion of the bounds for evoking the commonly used Michaelis-Menten rate framework as well as the existing constraints of spectroscopy, contrasted with microscale voltammetry.

  PublisherOA PDFDOI

• Rate and mechanism of thiolate deligation in Au ₂₅ nanoclusters <i>via in operando</i> electrochemical impedance spectroscopy

  Chemical Science · 2025-11-12

  articleOpen accessSenior authorCorresponding

  In operando electrochemical impedance spectroscopy provides in situ monitoring of the dynamic evolution of gold nanoclusters, offering mechanistic insight and kinetic quantification of their catalytic activation process: reductive deligation.

  PublisherOA PDFDOI

• Investigation of Noise at a Microelectrode during a Faradaic Reaction

  ACS electrochemistry. · 2025-02-22 · 4 citations

  articleOpen accessSenior authorCorresponding

  Measurement of small currents is often impeded by a suboptimal signal-to-noise ratio, largely due to background noise. This background noise significantly constrains the range of catalysts accessible for interrogation via micro- and nanoscale electrochemistry. In response, this work reveals how background noise scales in the presence of induced Faradaic reactions. We measured noise under a series of electrochemical conditions and discovered that the induced noise from a Faradaic reaction scales directly with current. Complementary electrochemical impedance spectroscopy measurements demonstrated that diffusional resistance dictates the noise of Faradaic reactions, independent of the electrochemical mechanism. The noise source is thermal in origin and propagates in a predictable trend, which is inversely proportional to the equivalent diffusional resistance of the analyte. The universality of the observed phenomenon allows for better deconvolution of measured charge from background noise, thus assisting in achieving higher resolution and measurement precision, which is a key in micro- and nanoscale electrochemical measurements.

  PublisherOA PDFDOI

• A Redox‐Tunable Carborane Crown: Toward Highly Selective Electrochemical Lithium Capture

  Chemistry - A European Journal · 2025-11-17 · 1 citations

  articleOpen access

  Abstract Lithium is a critical element with a projected exponential rise in demand due to its widespread use in battery energy storage. New methods to extract Li + , such as through membrane adsorption‐based direct Li + extraction (DLE) technologies, are at various stages of development and aim to separate Li + from brine and even seawater. In this report, we present a fundamentally new class of highly selective Li + ‐capture agent, the carborane‐crown compound, 1,2‐((6,6,7,7‐Me 4 )14‐crown‐4)‐ ortho ‐carborane ( 14C4 Cb ), which is electrochemically activated for strong, selective Li + binding over Na + and K + . This newly synthesized extractant features a redox‐tunable cavity size, giving rise to tunable binding constants for Li + capture, favorable coulombic interactions between the reduced anionic capture agent and the Li + cations, and boasts the benefit of rapid, electrochemically driven capture kinetics. Weak, negligible binding to Li + was observed in the neutral “ closo ” carborane state ( 14C4 Cb ), whereas strong binding was observed in the cage‐opened reduced nido state ( 14C4 Cb 2− ). Equilibrium ( K ) binding constants were measured through experimental and simulated voltammetry, yielding the following log K metal (experimental; simulation ) values: log K Li (6.8 ± 0.6; 8.0 ), log K Na (3.7 ± 0.2; 4.9 ), log K K (1.7 ± 0.2; 2.2 ). Rapid mass transport of Li + to the electrode surface resulted in the simulated value (log K Li = 8.0) representing a lower‐limit value for log K Li as described herein. The observed strong binding to Li + over Na + and K + is attributed to both the favorable redox‐tunable crown cavity size of the 14C4 Cb/ 14C4 Cb 2− couple, combined with strong coulombic interactions in the reduced nido state. This platform offers a potential new, rapid, and highly selective technique for Li + capture in next‐generation electrochemical DLE technologies.

  PublisherOA PDFDOI

Recent grants

• Bioelectrochemistry at the Nanoscale: Fundamentals and Applications

  NIH · $1.7M · 2021–2026

Frequent coauthors

• Richard G. Compton

  University of Oxford

  32 shared

• Stanislav V. Sokolov

  University of Oxford

  15 shared

• David Cahen

  Weizmann Institute of Science

  13 shared

• Israel Pecht

  12 shared

• Brian Roehrich

  12 shared

• Mordechai Sheves

  Weizmann Institute of Science

  12 shared

• Enno Kätelhön

  University of Art and Design Offenbach

  11 shared

• Julia Chung

  9 shared