Planar Bilayers Research Articles

Effects of Spontaneous Curvature on Interfacial Adsorption and Collapse of Phospholipid Monolayers.

To function effectively, pulmonary surfactant must adsorb rapidly to the alveolar air/water interface, but avoid collapse from the interface when compressed to low surface tensions. Prior studies show that phospholipids in the cylindrical monolayers of the inverse hexagonal (HII) phase adsorb quickly. The monolayers have negative curvature, defined by the concave shape of the hydrophilic face. Formation of the HII structures, however, involves significant disruption of optimal chain-packing. Samples with significant spontaneous curvature, formed in the absence of applied force, may nonetheless have lamellar structures. The experiments here tested whether planar lamellar bilayers formed by phospholipids with negative spontaneous curvature might adsorb rapidly but collapse slowly. Prior studies have shown that binary mixtures of dioleoyl phosphatidylcholine-dioleoyl phosphatidylethanolamine (DOPC-DOPE) with higher mol fractions of DOPE (XPE) have more negative spontaneous curvature. Samples with higher XPE adsorbed more rapidly but also collapsed more quickly. Over that range of XPE, small angle X-ray scattering showed only lamellar structures. The HII phase was undetectable. The results suggest that the innate tendency of the phospholipids to form curved structures has primary importance for adsorption rather than the presence of HII structures. Planar structures are insufficient to minimize the tendency of spontaneous curvature to promote collapse. These findings are consistent with adsorption and collapse that occur via rate-limiting structures with significant negative curvature.

Mechanical characterization of freestanding lipid bilayers with temperature-controlled phase.

Coexistence of lipid domains in cell membranes is associated with vital biological processes. Here, we investigate two such membranes: a multi-component membrane composed of DOPC and DPPC lipids with gel and fluid separated domains, and a single component membrane composed of PMPC lipids forming ripples. We characterize their mechanical properties below their melting point, where ordered and disordered regions coexist, and above their melting point, where they are in fluid phase. To conduct these inquiries, we create lipid bilayers in a microfluidic chip interfaced with a heating system and optical tweezers. The chip features a bubble trap and enables high-throughput formation of planar bilayers. Optical tweezers experiments reveal interfacial hydrodynamics (fluid-slip) and elastic properties (membrane tension and bending rigidity) at various temperatures. For PMPC bilayers, we demonstrate a higher fluid slip at the interface in the fluid-phase compared to the ripple phase, while for the DOPC:DPPC mixture, similar fluid slip is measured below and above the transition point. Membrane tension for both compositions increases after thermal fluidization. Bending rigidity is also measured using the forces required to extend a lipid nanotube pushed out of the freestanding membranes. This novel temperature-controlled microfluidic platform opens numerous possibilities for thermomechanical studies on freestanding planar membranes.

Unveiling the optoelectronic properties of bulk, monolayer, and bilayer TiS2: A DFT approach

Over the years, there has been significant research aimed at improving the performance of titanium disulfides (TiS2) in a wide range of applications, including lubricants, batteries, thermoelectric and electronic devices, catalysts, superconductors, photovoltaic devices, and more. This work investigates the optoelectronic properties of TiS2 using Density Functional Theory (DFT) calculations. The slab models were constructed for bulk, bilayer, and monolayer TiS2 (001) planes based on the 1T-TiS2 hexagonal phase. The GGA-PBE functional yielded the most accurate bandgaps: 0.178 eV (bulk), 0.047 eV (bilayer), and 0.112 eV (monolayer). The calculated lattice constants for bulk TiS2 with GGA-PBE were a = b = 3.407 Å and c = 5.697 Å, with an equilibrium volume of 57.24 ų. Electronic density of states (DOS) analysis revealed semiconducting behavior for both bulk and monolayer TiS2, with dominant peaks at the valence band. Bilayer TiS2 exhibited a higher DOS in the conduction band, indicating a more conductor-like character. Light absorption calculations showed the strongest peak for bilayer TiS2 (∼610,000 cm⁻¹ at 14.8 eV), followed by monolayer (∼13 eV) and bulk (∼12 eV). These results suggest that bulk TiS2 is preferable for applications requiring superior electrical properties, while bilayer TiS2 is more advantageous for applications focusing on light capture.

The role of N-terminal acetylation of COVID fusion peptides in the interactions with liquid-ordered lipid bilayers

The partitioning of viral fusion peptides in lipid membranes with varying order was investigated due to the fusion mechanism being a potential therapeutic approach. Using a planar bilayer model and advanced techniques such as neutron reflectometry (NR) and quartz crystal microbalance with dissipation (QCM-D) the structural aspects of peptide-lipid interactions were explored. The study focused on two target membranes: one forming a liquid-ordered domain and the other forming a liquid-disordered domain. Surprisingly, the COVID fusion peptides did not bind significantly to either membrane, as demonstrated by both QCM-D and NR data, suggesting negligible or no interaction with the bilayer. However, the acetylated COVID fusion peptide showed distinct behaviour, indicating a crucial role of N-terminal acetylation in binding to cholesterol-rich liquid-ordered domains. The acetylated peptide induced changes in the structure and thickness of the SM/DPPS/Chol bilayer whereas proteins and peptides commonly only bind to disordered phases. This study provides valuable insights into the mechanisms of viral membrane fusion and highlights the importance of acetylation in influencing peptide-lipid interactions, laying the groundwork for potential antiviral therapeutic strategies.

Characterization of a novel Ca2+-Activated potassium channel in rat brain rough endoplasmic reticulum

ObjectivesPotassium channels in the endoplasmic reticulum (ER) are crucial for maintaining calcium balance during calcium fluxes. Disruption in ER calcium balance leads to ER stress, implicated in diseases like diabetes and Alzheimer's disease (AD). However, limited data exists on ER potassium channels in excitable tissues such as the brain. To fill this gap, we aimed to evaluate potassium currents in rat brain rough endoplasmic reticulum (RER). MethodsRats were euthanized under deep anesthesia and their brains were immediately removed. The brains were then homogenized in ice-cold sucrose buffer, followed by the extraction of RER microsomes through a series of centrifugation processes. Purity of sample was evaluated using western blotting technique. Single channel recordings were done in voltage steps from +50 to −60 mV following incorporation of rat brain RER vesicles into planar bilayers. ResultsWe observed a voltage-dependent potassium channel with an approximate conductance of 188 pS. Channel open probability was low at negative voltages, increasing at positive voltages. The channel was blocked by Charybdotoxin but not by Iberiotoxin. Additionally, TRAM-34, a specific KCa3.1 channel blocker, suppressed channel current amplitude and open probability. Western blot analysis revealed specific bands for anti-KCa3.1 antibody, approximately 50 kDa in brain homogenate and RER fraction. ConclusionOur study provides strong evidence for the presence of an KCa3.1 channel on the RER membrane in rat brain, exhibiting distinct electro-pharmacological profile compared to plasma membrane and other organelles.

Exploring the Properties of Curved Lipid Membranes: Comparative Analysis of Atomistic and Coarse-Grained Force Fields.

Curvature emerges as a fundamental membrane characteristic crucial for diverse biological processes, including vesicle formation, cell signaling, and membrane trafficking. Increasingly valuable insights into atomistic details governing curvature-dependent membrane properties are provided by computer simulations. Nevertheless, the underlying force field models are conventionally calibrated and tested in relation to experimentally derived parameters of planar bilayers, thereby leaving uncertainties concerning their consistency in reproducing curved lipid systems. In this study we compare the depiction of buckled phosphatidylcholine (POPC) and POPC-cholesterol membranes by four popular force field models. Aside from agreement with respect to general trends in curvature dependence of a number of parameters, we observe a few qualitative differences. Among the most prominent ones is the difference between atomistic and coarse grained force fields in their representation of relative compressibility of the polar headgroup region and hydrophobic lipid core. Through a number of downstream effects, this discrepancy can influence the way in which curvature modulates the behavior of membrane bound proteins depending on the adopted simulation model.

Viroporin-like activity of the hairpin transmembrane domain of African swine fever virus B169L protein.

African swine fever virus (ASFV) is the causative agent of a contagious disease affecting wild and domestic swine. The function of B169L protein, as a potential integral structural membrane protein, remains to be experimentally characterized. Using state-of-the-art bioinformatics tools, we confirm here earlier predictions indicating the presence of an integral membrane helical hairpin, and further suggest anchoring of this protein to the ER membrane, with both terminal ends facing the lumen of the organelle. Our evolutionary analysis confirmed the importance of purifying selection in the preservation of the identified domains during the evolution of B169L in nature. Also, we address the possible function of this hairpin transmembrane domain (HTMD) as a class IIA viroporin. Expression of GFP fusion proteins in the absence of a signal peptide supported B169L insertion into the ER as a Type III membrane protein and the formation of oligomers therein. Overlapping peptides that spanned the B169L HTMD were reconstituted into ER-like membranes and the adopted structures analyzed by infrared spectroscopy. Consistent with the predictions, B169L transmembrane sequences adopted α-helical conformations in lipid bilayers. Moreover, single vesicle permeability assays demonstrated the assembly of lytic pores in ER-like membranes by B169L transmembrane helices, a capacity confirmed by ion-channel activity measurements in planar bilayers. Emphasizing the relevance of these observations, pore-forming activities were not observed in the case of transmembrane helices derived from EP84R, another ASFV protein predicted to anchor to membranes through a α-helical HTMD. Overall, our results support predictions of viroporin-like function for the B169L HTMD.IMPORTANCEAfrican swine fever (ASF), a devastating disease affecting domestic swine, is widely spread in Eurasia, producing significant economic problems in the pork industry. Approaches to prevent/cure the disease are mainly restricted to the limited information concerning the role of most of the genes encoded by the large (160-170 kba) virus genome. In this report, we present the experimental data on the functional characterization of the African swine fever virus (ASFV) gene B169L. Data presented here indicates that the B169L gene encodes for an essential membrane-associated protein with a viroporin function.

Multifaceted Activity of Fabimycin: Insights from Molecular Dynamics Studies on Bacterial Membrane Models.

Membranes─cells' essential scaffolds─are valid molecular targets for substances with an antimicrobial effect. While certain substances, such as octenidine, have been developed to target membranes for antimicrobial purposes, the recently reported molecule, fabimycin (F2B)─a novel agent targeting drug-resistant Gram-negative bacteria─has not received adequate attention regarding its activity on membranes in the literature. The following study aims to investigate the effects of F2B on different bacterial membrane models, including simple planar bilayers and more complex bilayer systems that mimic the Escherichia coli shell equipped with double inner and outer bilayers. Our results show that F2B exhibited more pronounced interactions with bacterial membrane systems compared to the control PC system. Furthermore, we observed significant changes in local membrane property homeostasis in both the inner and outer membrane models, specifically in the case of lateral diffusion, membrane thickness, and membrane resilience (compressibility, tilt). Finally, our results showed that the effect of F2B differed in a complex system and a single membrane system. Our study provides new insights into the multifaceted activity of F2B, demonstrating its potential to disrupt bacterial membrane homeostasis, indicating that its activity extends the currently known mechanism of FabI enzyme inhibition. This disruption, coupled with the ability of F2B to penetrate the outer membrane layers, sheds new light on the behavior of this antimicrobial molecule. This highlights the importance of the interaction with the membrane, crucial in combating bacterial infections, particularly those caused by drug-resistant strains.

Studying the Effects of Dissolved Noble Gases and High Hydrostatic Pressure on the Spherical DOPC Bilayer Using Molecular Dynamic Simulations.

Fine-grained molecular dynamics simulations have been conducted to depict lipid objects enclosed in water and interacting with a series of noble gases dissolved in the medium. The simple point-charge (SPC) water system, featuring a boundary composed of 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) molecules, maintained stability throughout the simulation under standard conditions. This allowed for the accurate modeling of the effects of hydrostatic pressure at an ambient pressure of 25 bar. The chosen pressure references the 240 m depth of seawater: the horizon frequently used by commercial divers, who comprise the primary patient population of the neurological complication of inert gas narcosis and the consequences of high-pressure neurological syndrome. To quantify and validate the neurological effects of noble gases and discriminate them from high hydrostatic pressure, we reduced the dissolved gas molar concentration to 1.5%, three times smaller than what we previously tested for the planar bilayer (3.5%). The nucleation and growth of xenon, argon and neon nanobubbles proved consistent with the data from the planar bilayer simulations. On the other hand, hyperbaric helium induces only a residual distorting effect on the liposome, with no significant condensed gas fraction observed within the hydrophobic core. The bubbles were distributed over a large volume-both in the bulk solvent and in the lipid phase-thereby causing substantial membrane distortion. This finding serves as evidence of the validity of the multisite distortion hypothesis for the neurological effect of inert gases at high pressure.

A Halogen‐Bond‐Driven Artificial Chloride‐Selective Channel Constructed from 5‐Iodoisophthalamide‐based Molecules

AbstractDespite considerable emphasis on advancing artificial ion channels, progress is constrained by the limited availability of small molecules with the necessary attributes of self‐assembly and ion selectivity. In this study, a library of small molecules based on 5‐haloisophthalamide and a non‐halogenated isophthalamide were examined for their ion transport properties across the lipid bilayer membranes, and the finding demonstrates that the di‐hexyl‐substituted 5‐iodoisophthalamide derivative exhibits the highest level of activity. Furthermore, it was established that the highest active compound facilitates the selective chloride transport that occurs via an antiport‐mediated mechanism. The crystal structure of the compound unveils a distinctive self‐assembly of molecules, forming a zig‐zag channel pore that is well‐suited for the permeation of anions. Planar bilayer conductance measurements proved the formation of chloride selective channels. A molecular dynamics simulation study, relying on the self‐assembled component derived from the crystal structure, affirmed the paramount significance of intermolecular hydrogen bonding in the formation of supramolecular barrel‐rosette structures that span the bilayer. Furthermore, it was demonstrated that the transport of chloride across the lipid bilayer membrane is facilitated by the synergistic effects of halogen bonding and hydrogen bonding within the channel.

A Halogen-Bond-Driven Artificial Chloride-Selective Channel Constructed from 5-Iodoisophthalamide-based Molecules.

Despite considerable emphasis on advancing artificial ion channels, progress is constrained by the limited availability of small molecules with the necessary attributes of self-assembly and ion selectivity. In this study, a library of small molecules based on 5-haloisophthalamide and a non-halogenated isophthalamide were examined for their ion transport properties across the lipid bilayer membranes, and the finding demonstrates that the di-hexyl-substituted 5-iodoisophthalamide derivative exhibits the highest level of activity. Furthermore, it was established that the highest active compound facilitates the selective chloride transport that occurs via an antiport-mediated mechanism. The crystal structure of the compound unveils a distinctive self-assembly of molecules, forming a zig-zag channel pore that is well-suited for the permeation of anions. Planar bilayer conductance measurements proved the formation of chloride selective channels. A molecular dynamics simulation study, relying on the self-assembled component derived from the crystal structure, affirmed the paramount significance of intermolecular hydrogen bonding in the formation of supramolecular barrel-rosette structures that span the bilayer. Furthermore, it was demonstrated that the transport of chloride across the lipid bilayer membrane is facilitated by the synergistic effects of halogen bonding and hydrogen bonding within the channel.

Methylation of Phenyl Rings in Ester-Stabilized Phosphorus Ylides Vastly Enhances Their Protonophoric Activity.

We have recently discovered that ester-stabilized phosphorus ylides, resulting from deprotonation of a phosphonium salt such as [Ph3PCH2COOR], can transfer protons across artificial and biological membranes. To create more effective cationic protonophores, we synthesized similar phosphonium salts with one ((heptyloxycarbonylmethyl)(p-tolyl)bromide) or two ((butyloxycarbonylmethyl)(3,5-xylyl)osphonium bromide) methyl substituents in the phenyl groups. The methylation enormously augmented both protonophoric activity of the ylides on planar bilayer lipid membrane (BLM) and uncoupling of mammalian mitochondria, which correlated with strongly accelerated flip-flop of their cationic precursors across the BLM.

Design and Construction of a Multi-Tiered Minimal Actin Cortex for Structural Support in Lipid Bilayer Applications.

Artificial lipid bilayers have revolutionized biochemical and biophysical research by providing a versatile interface to study aspects of cell membranes and membrane-bound processes in a controlled environment. Artificial bilayers also play a central role in numerous biosensing applications, form the foundational interface for liposomal drug delivery, and provide a vital structure for the development of synthetic cells. But unlike the envelope in many living cells, artificial bilayers can be mechanically fragile. Here, we develop prototype scaffolds for artificial bilayers made from multiple chemically linked tiers of actin filaments that can be bonded to lipid headgroups. We call the interlinked and layered assembly a multiple minimal actin cortex (multi-MAC). Construction of multi-MACs has the potential to significantly increase the bilayer's resistance to applied stress while retaining many desirable physical and chemical properties that are characteristic of lipid bilayers. Furthermore, the linking chemistry of multi-MACs is generalizable and can be applied almost anywhere lipid bilayers are important. This work describes a filament-by-filament approach to multi-MAC assembly that produces distinct 2D and 3D architectures. The nature of the structure depends on a combination of the underlying chemical conditions. Using fluorescence imaging techniques in model planar bilayers, we explore how multi-MACs vary with electrostatic charge, assembly time, ionic strength, and type of chemical linker. We also assess how the presence of a multi-MAC alters the underlying lateral diffusion of lipids and investigate the ability of multi-MACs to withstand exposure to shear stress.

Synthesis of Triphenylphosphonium-Linked Derivative of 3,5-Ditert-butyl-4-hydroxybenzylidene-malononitrile (SF6847) via Knoevenagel Reaction Yields an Effective Mitochondria-Targeted Protonophoric Uncoupler.

Mitochondrial uncouplers are actively sought as potential therapeutics. Here, we report the first successful synthesis of mitochondria-targeted derivatives of the highly potent uncoupler 3,5-ditert-butyl-4-hydroxybenzylidene-malononitrile (SF6847), bearing a cationic alkyl(triphenyl)phosphonium (TPP) group. As a key step of the synthesis, we used condensation of a ketophenol with malononitrile via the Knoevenagel reaction. SF-C5-TPP with a pentamethylene linker between SF6847 and TPP, stimulating respiration and collapsing membrane potential of rat liver mitochondria at submicromolar concentrations, proved to be the most effective uncoupler of the series. SF-C5-TPP showed pronounced protonophoric activity on a model planar bilayer lipid membrane. Importantly, SF-C5-TPP exhibited rather low toxicity in fibroblast cell culture, causing mitochondrial depolarization in cells at concentrations that only slightly affected cell viability. SF-C5-TPP was more effective in decreasing the mitochondrial membrane potential in the cell culture than SF6847, in contrast to the case of isolated mitochondria. Like other zwitterionic uncouplers, SF-C5-TPP inhibited the growth of Bacillus subtilis in the micromolar concentration range.

Planar Bilayer PT-Symmetric Systems and Resonance Energy Transfer

Parity-time (PT) symmetry provides an outstanding improvement of photonic devices’ performance due to the remarkable physics behind it. Resonance energy transfer (RET) as an important characteristic mediating the molecules that can be tailored in the PT-symmetric environment, too. We study how planar bilayer PT-symmetric systems affect the process of resonance energy transfer occurring in the vicinity thereof. First, we investigate the reflectance and transmittance spectra of such systems by calculating reflection and transmission coefficients as well as total radiation amplification as functions of medium parameters. We obtain that reflectance and total amplification are greatest near the exceptional points of the PT-symmetric system. Then, we perform numerical calculations of the RET rate and investigate its dependence on the complex permittivity of the PT-symmetric medium, dipole orientation, frequency of radiation and layer thickness. Optically thick PT-symmetric systems may operate at lower gain at the expense of the appearance of chaotic-like behaviors. These appear owing to the dense oscillations in the reflectance and transmittance spectra and vividly manifest themselves as stochastic-like positions of the exceptional points for PT-symmetric bilayers. The RET rate, being a result of the field interference, can be significantly amplified and suppressed near exceptional points exhibiting a Fano-like lineshape.

Photolipid excitation triggers depolarizing optocapacitive currents and action potentials

Optically-induced changes in membrane capacitance may regulate neuronal activity without requiring genetic modifications. Previously, they mainly relied on sudden temperature jumps due to light absorption by membrane-associated nanomaterials or water. Yet, nanomaterial targeting or the required high infrared light intensities obstruct broad applicability. Now, we propose a very versatile approach: photolipids (azobenzene-containing diacylglycerols) mediate light-triggered cellular de- or hyperpolarization. As planar bilayer experiments show, the respective currents emerge from millisecond-timescale changes in bilayer capacitance. UV light changes photolipid conformation, which awards embedding plasma membranes with increased capacitance and evokes depolarizing currents. They open voltage-gated sodium channels in cells, generating action potentials. Blue light reduces the area per photolipid, decreasing membrane capacitance and eliciting hyperpolarization. If present, mechanosensitive channels respond to the increased mechanical membrane tension, generating large depolarizing currents that elicit action potentials. Membrane self-insertion of administered photolipids and focused illumination allows cell excitation with high spatiotemporal control.

Effects of diverse short-chain alcohols on vesicular fusion with a planar bilayer

Effects of diverse short-chain alcohols on vesicular fusion with a planar bilayer

Extracellular membrane vesicles derived from Komagataeibacter oboediens exposed on the International Space Station fuse with artificial eukaryotic membranes in contrast to vesicles of reference bacterium

Membranous Extracellular Vesicles (EVs) of Gram-negative bacteria are a secretion and delivery system that can disseminate bacterial products and interact with hosts and the environment. EVs of nonpathogenic bacteria deliver their contents by endocytosis into eukaryotic cells, however, no evidence exists for a fusion delivery mechanism. Here, we describe the fusion of exposed to space/Mars-like stressors simulated on the International Space Station vesicles (E-EVs) from Komagataeibacter oboediens to different types of model planar membranes in comparison with the EVs of the ground-based reference strain. The most reliable fusion was achieved with PC:PE:ergosterol or sterol-free PC:PE bilayers. The relative permeability ratio (PK+/PCl-) estimated from the shift of zero current potential according to Goldman–Hodgkin–Katz equation consisted of 4.17 ± 0.48, which coincides with preferential cation selectivity of the EV endogenous channels. The increase in membrane potential from 50 mV to 100 mV induced the fusion of E-EVs with all tested lipid compositions. The fusion of model exosomes with planar bilayer lipid membranes was confirmed by separate step-like increases in its conductance. In contrast, the ground-based reference K. oboediens EVs never induced the fusion event. In our study, we show membrane lipidome perturbations and increased protein aggregation occurred in the exposed samples in the harsh environment when outer membranes of K. oboediens acquired the capability of both homo- and heterotypic fusion possibly by altered membrane fluidity and the pore-forming capability.

Membrane Condensation and Curvature Induced by SARS-CoV-2 Envelope Protein.

The envelope (E) protein of SARS-CoV-2 participates in virion encapsulation and budding at the membrane of the endoplasmic reticulum Golgi intermediate compartment (ERGIC). The positively curved membrane topology required to fit an 80 nm viral particle is energetically unfavorable; therefore, viral proteins must facilitate ERGIC membrane curvature alteration. To study the possible role of the E protein in this mechanism, we examined the structural modification of the host lipid membrane by the SARS-CoV-2 E protein using synchrotron-based X-ray methods. Our reflectometry results on solid-supported planar bilayers show that E protein markedly condenses the surrounding lipid bilayer. For vesicles, this condensation effect differs between the two leaflets such that the membrane becomes asymmetric and increases its curvature. The formation of such a curved and condensed membrane is consistent with the requirements to stably encapsulate a viral core and supports a role for E protein in budding during SARS-CoV-2 virion assembly.

Nanoparticles of Push-Pull Triphenylamine-Based Molecules for Light-Controlled Stimulation of Neuronal Activity.

Organic semiconductor materials with a unique set of properties are very attractive for interfacing biological objects and can be used for noninvasive therapy or detection of biological signals. Here, we describe the synthesis and investigation of a novel series of organic push-pull conjugated molecules with the star-shaped architecture, consisting of triphenylamine as a branching electron donor core linked through the thiophene π-spacer to electron-withdrawing alkyl-dicyanovinyl groups. The molecules could form stable aqueous dispersions of nanoparticles (NPs) without the addition of any surfactants or amphiphilic polymer matrixes with the average size distribution varying from 40 to 120 nm and absorption spectra very similar to those of human eye retina pigments such as rods and green cones. Variation of the terminal alkyl chain length of the molecules forming NPs from 1 to 12 carbon atoms was found to be an efficient tool to modulate their lipophilic and biological properties. Possibilities of using the NPs as light nanoactuators in biological systems or as artificial pigments for therapy of degenerative retinal diseases were studied both on the model planar bilayer lipid membranes and on the rat cortical neurons. In the planar bilayer system, the photodynamic activity of these NPs led to photoinactivation of ion channels formed by pentadecapeptide gramicidin A. Treatment of rat cortical neurons with the NPs caused depolarization of cell membranes upon light irradiation, which could also be due to the photodynamic activity of the NPs. The results of the work gave more insight into the mechanisms of light-controlled stimulation of neuronal activity and for the first time showed that fine-tuning of the lipophilic affinity of NPs based on organic conjugated molecules is of high importance for creating a bioelectronic interface for biomedical applications.