Double-stranded DNA Research Articles

Panax notoginseng Saponins Ameliorate Gamma Radiation-Mediated Damages in Human Peripheral Blood Monocytes and Swiss Albino Mice.

In this study, the protective effects of Panax notoginseng saponins (PNS) against gamma radiation-induced DNA damage and associated physiological alterations in Swiss albino mice were investigated. Exposure to gamma radiation led to a dose-dependent increase in cytokinesis-blocked micronuclei (CBMN) double-strand DNA breaks (DSBs), dicentric aberrations (DC), formation in peripheral blood mononuclear cells. However, pretreatment with PNS at concentrations of 1, 5, and 10 µg/mL significantly attenuated the frequencies of DC and CBMN in a concentration-dependent manner. PNS administration before radiation exposure also reduced radiation-induced DSBs in BL, indicating protection against reactive oxygen species generation and DNA damage. Notably, pretreatment with PNS at 10 µg/mL prevented the overexpression of γ-H2AX, proteins associated with DNA damage response, in irradiated mice. In addition, in vivo studies showed intraperitoneal administration of PNS (25 mg/kg body weight) for 1 h before radiation exposure mitigated lipid peroxidation levels and restored antioxidant status, countering oxidative damage induced by gamma radiation. Furthermore, PNS pretreatment reversed the decrease in hemoglobin (Hb) content, white blood cell count, and red blood cell count in irradiated mice, indicating preservation of hematological parameters. Overall, PNS demonstrated an anticlastogenic effect by modulating radiation-induced DSBs and preventing oxidative damage, thus highlighting its potential as a protective agent against radiation-induced DNA damage and associated physiological alterations. Clinically, PNS will be beneficial for cancer patients undergoing radiotherapy, but their pharmacological properties and toxicity profiles need to be studied.

Directly Characterizing the Capture Radius of Tethered Double-Stranded DNA by Single-Molecule Nanopipette Manipulation.

The tethered molecule exhibits characteristics of both free and fixed states, with the electrodynamics involved in its diffusion, electrophoresis, and stretching processes still not fully understood. We developed a Single-Molecule Manipulation, Identification, and Length Examination (SMILE) system by integrating piezoelectric devices with nanopipettes. This system enabled successful capture and stretching of tethered double-stranded DNA within the nanopore. Our research unveiled distinct capture (rcapture) and stretch radii (rstretch) surrounding the DNA's anchor point. Notably, consistent ratios of capture radius for DNA of varying lengths (2k, 4k, and 6k base pairs) were observed across different capturing voltages, approximately 1:1.4:1.83, showing a resemblance to their gyration radius ratios. However, the ratios of stretch radius are consistent to their contour length (L0), with the stretching ratio (rstretch/L0) increasing from 70 to 90% as the voltage rose from 100 to 1000 mV. Additionally, through numerical simulations, we identified the origin of capture and stretch radii, determined by the entropic elasticity-induced capture barrier and the electric field-dominant escape barrier. This research introduces an innovative methodology and outlines research perspectives for a comprehensive exploration of the conformational, electrical, and diffusion characteristics of tethered molecules.

Synergistic effect of split DNA activators of Cas12a with exon-unwinding and induced targeting effect.

CRISPR-Cas12a, an RNA-guided nuclease, has been repurposed for genome editing and molecular diagnostics due to its capability of cis-cleavage on target DNA and trans-cleavage on non-target single-strand DNA (ssDNA). However, the mechanisms underlying the activation of trans-cleavage activity of Cas12a, particularly in the context of split DNA activators, remain poorly understood. We elucidate the synergistic effect of these activators and introduce the concepts of induced targeting effect and exon-unwinding to describe the phenomenon. We demonstrate that upon binding of split DNA activators adjacent to the Protospacer Adjacent Motif (PAM) to the Cas12a ribonucleoprotein (Cas12a-RNP), a ternary complex form that can capture and interact with distal split DNA activators to achieve synergistic effects. Notably, if the distal activator is double-strand DNA (dsDNA), the complex initiates exon-unwinding, facilitating the RNA-guide sequence's access. Our findings provide a mechanistic insight into action of Cas12a and propose a model that could significantly advance our understanding of its function.

Modulating the DNA/Lipid Interface through Multivalent Hydrophobicity.

Lipids and nucleic acids are two of the most abundant components of our cells, and both molecules are widely used as engineering materials for nanoparticles. Here, we present a systematic study of how hydrophobic modifications can be employed to modulate the DNA/lipid interface. Using a series of DNA anchors with increasing hydrophobicity, we quantified the capacity to immobilize double-stranded (ds) DNA to lipid membranes in the liquid phase. Contrary to electrostatic effects, hydrophobic anchors are shown to be phase-independent if sufficiently hydrophobic. For weak anchors, the overall hydrophobicity can be enhanced following the concept of multivalency. Finally, we demonstrate that structural flexibility and anchor orientation overrule the effect of multivalency, emphasizing the need for careful scaffold design if strong interfaces are desired. Together, our findings guide the design of tailored DNA/membrane interfaces, laying the groundwork for advancements in biomaterials, drug delivery vehicles, and synthetic membrane mimics for biomedical research and nanomedicine.

Genomic Characterization of Phage ZP3 and Its Endolysin LysZP with Antimicrobial Potential against Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae (Xoo) is a significant bacterial pathogen responsible for outbreaks of bacterial leaf blight in rice, posing a major threat to rice cultivation worldwide. Effective management of this pathogen is crucial for ensuring rice yield and food security. In this study, we identified and characterized a novel Xoo phage, ZP3, isolated from diseased rice leaves in Zhejiang, China, which may offer new insights into biocontrol strategies against Xoo and contribute to the development of innovative approaches to combat bacterial leaf blight. Transmission electron microscopy indicated that ZP3 had a short, non-contractile tail. Genome sequencing and bioinformatic analysis showed that ZP3 had a double-stranded DNA genome with a length of 44,713 bp, a G + C content of 52.2%, and 59 predicted genes, which was similar to other OP1-type Xoo phages belonging to the genus Xipdecavirus. ZP3's endolysin LysZP was further studied for its bacteriolytic action, and the N-terminal transmembrane domain of LysZP is suggested to be a signal-arrest-release sequence that mediates the translocation of LysZP to the periplasm. Our study contributes to the understanding of phage-Xoo interactions and suggests that phage ZP3 and its endolysin LysZP could be developed into biocontrol agents against this phytopathogen.

Entropy-driven amplification reaction and the CRISPR/Cas12a system form the basis of an electrochemical biosensor for E.coli-specific detection

We present an innovative biosensor designed for the precise identification of Escherichia coli (E.coli), a predominant pathogen responsible for gastrointestinal infections. E.coli is prevalent in environments characterized by substandard water quality and can lead to severe diarrhea, especially in hospital settings. The device employs entropy-driven reactions to synthesize copious amounts of double-stranded DNA (dsDNA), which, upon binding with crRNA, triggers the CRISPR/Cas12a system’s cleavage mechanism. This process results in the separation of a ferrocene (Fc)-tagged DNA strand from the electrode, enhancing the electrochemical signal for E.coli’s rapid and accurate detection. Our tests confirm the biosensor’s ability to quantify E.coli across a dynamic range from 100 to 10 million CFU/mL, achieving a detection threshold of just over 5 CFU/mL. The development of this electrochemical biosensor highlights its exceptional selectivity, high sensitivity, and user-friendly interface for E.coli detection. It stands as a significant step forward in pathogen detection technology, promising new directions for identifying various bacterial infections through the CRISPR/Cas mechanism.

Complete genome sequences of 12 lytic phages against multidrug-resistant Enterococcus faecalis.

We report the genome sequences of 12 Enterococcus faecalis phages isolated in Kenya, belonging to the genus Copernicusvirus, Efquatrovirus, Saphexavirus, and Kochikohdavirus. They have double-stranded DNA with lengths varying from 17,979 to 147,374 bp and G+C content from 33.14% to 40.05%. The genomes contain 28-250 coding sequences.

Different DNA Binding and Damage Mode between Anticancer Antibiotics Trioxacarcin A and LL-D49194α1.

Trioxacarcin A (TXN) is a highly potent cytotoxic antibiotic with remarkable structural complexity. The crystal structure of TXN bound to double-stranded DNA (dsDNA) suggested that the TXN interaction might depend on positions of two sugar subunits on the minor and major grooves of dsDNA. LL-D49194α1 (LLD) is a TXN analogue bearing the same polycyclic polyketide scaffold with a distinct glycosylation pattern. Although LLD was in a phase I clinical trial, how LLD binds to dsDNA remains unclear. Here, we solved the solution structures at high resolutions of palindromic 2″-fluorine-labeled guanine-containing duplex d(A1A2C3C4GFGFT7T8)2 and of its stable LLD and TXN covalently bound complexes. Combined with biochemical assays, we found that TXN-alkylated dsDNA would tend to keep DNA helix conformation, while LLD-alkylated dsDNA lost its stability more than TXN-alkylated dsDNA, leading to dsDNA denaturation. Thus, despite lower cytotoxicity in vitro, the differences of sugar substitutions in LLD caused greater DNA damage than TXN, thereby bringing about a completely new biological effect.

Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that encodes numerous cellular homologs, including cyclin D, G protein-coupled protein, interleukin-6, and macrophage inflammatory proteins 1 and 2. KSHV vCyclin encoded by ORF72, is the homolog of cellular cyclinD2. KSHV vCyclin can regulate virus replication and cell proliferation by constitutively activating cellular cyclin-dependent kinase 6 (CDK6). However, the regulatory mechanism of KSHV vCyclin has not been fully elucidated. In the present study, we identified a host protein named protein arginine methyltransferase 5 (PRMT5) that interacts with KSHV vCyclin. We further demonstrated that PRMT5 is upregulated by latency-associated nuclear antigen (LANA) through transcriptional activation. Remarkably, knockdown or pharmaceutical inhibition (using EPZ015666) of PRMT5 inhibited the cell cycle progression and cell proliferation of KSHV latently infected tumor cells. Mechanistically, PRMT5 methylates vCyclin symmetrically at arginine 128 and stabilizes vCyclin in a methyltransferase activity-dependent manner. We also show that the methylation of vCyclin by PRMT5 positively regulates the phosphorylate retinoblastoma protein (pRB) pathway. Taken together, our findings reveal an important regulatory effect of PRMT5 on vCyclin that facilitates cell cycle progression and proliferation, which provides a potential therapeutic target for KSHV-associated malignancies.

Controlling phase separations and reactions in trapped microfluidic droplets

Microfluidics and droplet-based assays are the basis for numerous high-throughput experiments, including bio-inspired microreactors and selection platforms for directed evolution. While elaborate techniques are available for the production of picoliter-sized droplets, there is an increasing demand for subsequent manipulation and control of the droplet interior. Here, we report on a straightforward method to rapidly adjust the size of single to several hundred double-emulsion droplets in a microfluidic sieve by varying the carrier fluid’s salt concentration. We show that the concomitant concentration changes in the droplet interior can drive a reversible demixing transition in a biomimetic binary fluid. As another application, we show that growing and shrinking of trapped droplets can be utilized to achieve a reversible dissociation of double-stranded DNA into single strands, i.e. cycles of reversible DNA hybridization, similar to PCR cycles, can be achieved by reversibly changing the droplet size at constant temperature. Altogether, our approach shows how a simple and temporally tunable manipulation of the size and the chemistry in prefabricated droplets can be achieved by an external control parameter.

Complete genome sequences of four lytic bacteriophages against multidrug-resistant Enterococcus faecium.

We report the genome sequences of four Enterococcus faecium phages isolated from environmental wastewater in Kenya. They are double-stranded DNA phages with genomes varying in length from 42,231 to 43,348 bp, with G+C contents ranging from 34.96% to 35.2%. The genomes contain 78-82 coding sequences.

GbHSP90 act as a dual functional role regulated in telomere stability in Ginkgo biloba

The heat shock protein 90 (HSP90) family members are not only widely involved in animal cellular immune response and signal transduction pathway regulation, but also play an important role in plant development and environmental stress response. Here,we identified a HSP90 family member in Ginkgo biloba, designated as GbHSP90, which performs a dual functional role to regulate telomere stability. GbHSP90 was screened by a yeast one-hybrid library using the Ginkgo biloba telomeric DNA (TTTAGGG)5. Fluorescence polarization, surface plasmon resonance(SPR) and EMSA technologyies revealed a specific interaction between GbHSP90 and the double-stranded telomeric DNA via its N-CR region, with no affinity for the single-stranded telomeric DNA or human double-stranded telomeric DNA. Furthermore, yeast two-hybrid system and Split-LUC assay demonstrated that GbHSP90 can interacts with two telomere end-binding proteins:the ginkgo telomerase reverse transcriptase (GbTERT) and the ginkgo Structural Maintenance of Chromosomes protein 1 (GbSMC1). Overexpression of GbHSP90 in human 293 T and HeLa cells increased cell growth rate, the content of telomerase reverse transcriptase (TERT), and promote cell division and inhibit cell apoptosis. Our results indicated GbHSP90 have dually functions: as a telomere-binding protein that binds specifically to double-stranded telomeric DNA and as a molecular chaperone that modulates cell differentiation and apoptosis by binding to telomere protein complexes in Ginkgo biloba. This study contributes to a significantly understanding of the unique telomere complex structure and regulatory mechanisms in Ginkgo biloba, a long-lived tree species.

An “on-off” ratiometric electrochemiluminescence biosensor based on LSPR-enhanced by Ag@Au nanostructures combined with Pd NCs catalysing a single luminophore for MiRNA let-7a detection

In this study, we reported a ratiometric electrochemiluminescence (ECL) biosensor based on localized surface plasmon resonance (LSPR)-enhanced Ag@Au nanostructures combined with palladium nanoclusters (Pd NCs) catalyzing the luminol-gold nanoparticles (L-Au NPs). Firstly, L-Au NPs were synthesized, hydrogen peroxide (H2O2) was used as a co-reactant, and Ag@Au nanostructures acted as an LSPR source to enhance the initial signal at the anode. Next, with the help of strand displacement amplification (SDA), the trace target miRNA let-7a was able to be converted to a number of output DNA. And then the Visual DNA Strand Displacement (DSD) was used to evaluate the conversion efficiency of miRNA let-7a into output DNA, thereby verifying that the SDA achieved signal amplification in the construction of biosensor. It was thereafter experimentally verified that the first decrease in anodic signal was achieved by strand amplification based on magnetic beads and polymerase excitation. In contrast, Pd NCs were synthesized using double-stranded DNA (dsDNA) as a template and excited with a cathodic signal, while a second decrease of the anodic signal was also achieved. The developed ratiometric ECL biosensor demonstrated a sensitive detection of miRNA let-7a with a linear range from 0.1 pM to 10 aM and a detection limit of 5.45 aM (S/N = 3). In conclusion, the study presented a new idea for the construction of ratiometric ECL sensors based on a single luminophore, providing technical support for the early diagnosis of cancer.

Near zero background noise photoelectrochemical sensor based on sensitized signal probe CdS QDs-Dox intercalating double-stranded DNA for PEDV detection

The highly sensitive detection method for porcine epidemic diarrhea virus (PEDV) is crucial for promptly identify infected pigs and effectively control the spread of the virus. In this study, the sensitization enhancement of organic photoactive material was combined with near zero background noise strategy for PEDV sensitive detection. A novel sensitized signal probe CdS quantum dots-doxycycline complex (CdS QDs-Dox) was prepared serving as a photoelectrochemical (PEC) probe embedded in dsDNA. Subsequently, a thiol-modified upstream inner primer (SH-FIP) was immobilized on the surface of electrode modified with gold nanoparticles (Au NPs) via Au–S bonding, enabling the loop-mediated isothermal amplification (LAMP) of PEDV on the electrode surface. The PEC probe (CdS QDs-Dox) embedded in the amplified dsDNA groove showed an increasing photocurrent signal with the rise of PEDV concentration, establishing a near-zero background LAMP-PEC sensing platform for PEDV detection. Under optimized conditions, the photocurrent intensity of this platform exhibited a good linear relationship with PEDV concentrations ranging from 0.0005 pg/μL to 10 pg/μL, achieving a detection limit as low as 0.17 fg/μL. This platform demonstrates outstanding specificity and sensitivity, thereby enabling precise quantitative detection of diverse pathogens.

Recombinant thrombomodulin and recombinant antithrombin attenuate pulmonary endothelial glycocalyx degradation and neutrophil extracellular trap formation in ventilator-induced lung injury in the context of endotoxemia

BackgroundVascular endothelial damage is involved in the development and exacerbation of ventilator-induced lung injury (VILI). Pulmonary endothelial glycocalyx and neutrophil extracellular traps (NETs) are endothelial protective and damaging factors, respectively; however, their dynamics in VILI and the effects of recombinant thrombomodulin and antithrombin on these dynamics remain unclear. We hypothesized that glycocalyx degradation and NETs are induced by VILI and suppressed by recombinant thrombomodulin, recombinant antithrombin, or their combination.MethodsVILI was induced in male C57BL/6J mice by intraperitoneal lipopolysaccharide injection (20 mg/kg) and high tidal volume ventilation (20 mL/kg). In the intervention groups, recombinant thrombomodulin, recombinant antithrombin, or their combination was administered at the start of mechanical ventilation. Glycocalyx degradation was quantified by measuring serum syndecan-1, fluorescence-labeled lectin intensity, and glycocalyx-occupied area in the pulmonary vascular lumen. Double-stranded DNA in the bronchoalveolar fluid and fluorescent areas of citrullinated histone H3 and myeloperoxidase were quantified as NET formation.ResultsSerum syndecan-1 increased, and lectin fluorescence intensity decreased in VILI. Electron microscopy revealed decreases in glycocalyx-occupied areas within pulmonary microvessels in VILI. Double-stranded DNA levels in the bronchoalveolar lavage fluid and the fluorescent area of citrullinated histone H3 and myeloperoxidase in lung tissues increased in VILI. Recombinant thrombomodulin, recombinant antithrombin, and their combination reduced glycocalyx injury and NET marker levels. There was little difference in glycocalyx injury and NET makers between the intervention groups.ConclusionVILI induced glycocalyx degradation and NET formation. Recombinant thrombomodulin and recombinant antithrombin attenuated glycocalyx degradation and NETs in our VILI model. The effect of their combination did not differ from that of either drug alone. Recombinant thrombomodulin and antithrombin have the potential to be therapeutic agents for biotrauma in VILI.

Tumor microenvironment-responsive manganese-based nano-modulator activate the cGAS-STING pathway to enhance innate immune system response

BackgroundManganese ions (Mn2+) combined with adjuvants capable of damaging and lysing tumor cells form an antitumor nano-modulator that enhances the immune efficacy of cancer therapy through the cascade activation of the cyclic GMP-AMP interferon gene synthase-stimulator (cGAS-STING) pathway, which underscores the importance of developing antitumor nano-modulators, which induce DNA damage and augment cGAS-STING activity, as a critical future research direction.Methods and ResultsWe have successfully synthesized an antitumor nano-modulator, which exhibits good dispersibility and biosafety. This nano-modulator is engineered by loading manganese dioxide nanosheets (M-NS) with zebularine (Zeb), known for its immunogenicity-enhancing effects, and conducting targeted surface modification using hyaluronic acid (HA). After systemic circulation to the tumor site, Mn2+, Zeb, and reactive oxygen species (ROS) are catalytically released in the tumor microenvironment by H+ and H2O2. These components can directly or indirectly damage the DNA or mitochondria of tumor cells, thereby inducing programmed cell death. Furthermore, they promote the accumulation of double-stranded DNA (dsDNA) in the cytoplasm, enhancing the activation of the cGAS-STING signalling pathway and boosting the production of type I interferon and the secretion of pro-inflammatory cytokines. Additionally, Zeb@MH-NS enhances the maturation of dendritic cells, the infiltration of cytotoxic T lymphocytes, and the recruitment of natural killer cells at the tumor site.ConclusionsThis HA-modified manganese-based hybrid nano-regulator can enhance antitumor therapy by boosting innate immune activity and may provide new directions for immunotherapy and clinical translation in cancer.Graphical

Study on the electrochemical and spectroscopic characteristics of holmium ion and its interaction with DNA

Metal ion-DNA interactions play a crucial role in modulating the structure and function of genetic material in the natural environment. In this study, we report on the favorable electrochemical activity of holmium(III) (Ho3+) on a glassy carbon electrode (GCE) and its interaction with double-stranded DNA. The interaction between DNA and Ho3+ was investigated for the first time using cyclic voltammetry and differential pulse voltammetry. The electrochemical behavior of Ho3+ ions on a GCE exhibited a reversible electron transfer process, indicative of its redox activity. A linear correlation between the peak current and the square root of the scan rate was observed, suggesting a diffusion-controlled kinetic regime for the electrochemical process. Additionally, fluorescence and absorption spectroscopy were employed to confirm the binding of Ho3+ to DNA. Our findings demonstrate that, at pH 7.2, specific DNA bases and phosphate groups can interact with Ho3+ ions. Moreover, electrochemical measurements suggest that Ho3+ ions bind to DNA via a groove binding mode, with a calculated binding ratio of 1:1 between Ho3+ and DNA. Notably, under optimal conditions, an increase in the amount of DNA leads to a significant reduction in the current intensity of Ho3+ ions.

Identification of a novel DNA oxidative damage repair pathway, requiring the ubiquitination of the histone variant macroH2A1.1

BackgroundThe histone variant macroH2A (mH2A), the most deviant variant, is about threefold larger than the conventional histone H2A and consists of a histone H2A-like domain fused to a large Non-Histone Region responsible for recruiting PARP-1 to chromatin. The available data suggest that the histone variant mH2A participates in the regulation of transcription, maintenance of heterochromatin, NAD+ metabolism, and double-strand DNA repair.ResultsHere, we describe a novel function of mH2A, namely its implication in DNA oxidative damage repair through PARP-1. The depletion of mH2A affected both repair and cell survival after the induction of oxidative lesions in DNA. PARP-1 formed a specific complex with mH2A nucleosomes in vivo. The mH2A nucleosome-associated PARP-1 is inactive. Upon oxidative damage, mH2A is ubiquitinated, PARP-1 is released from the mH2A nucleosomal complex, and is activated. The in vivo-induced ubiquitination of mH2A, in the absence of any oxidative damage, was sufficient for the release of PARP-1. However, no release of PARP-1 was observed upon treatment of the cells with either the DNA alkylating agent MMS or doxorubicin.ConclusionsOur data identify a novel pathway for the repair of DNA oxidative lesions, requiring the ubiquitination of mH2A for the release of PARP-1 from chromatin and its activation.

Experimental, density functional theory and molecular docking studies about the interaction between 6-MP and DNA: A biosensor study

In the paper presents a new DNA biosensor including 6-Mercaptopurine (6-MP), a well-known anticancer drug. Interactions with single-stranded and double-stranded calf thymus DNA (ct ds DNA and ct ss DNA) of the mentioned drugs were checked via experimental and theoretical tools. The experimental part of the article includes the voltammetric analyses made to see the interaction between 6-MP and DNA. Impedance Spectroscopy (EIS) measurements were performed to evaluate changes in charge transfer resistance (Rct) due to interactions on the PGE surface. The limit of detection (LOD) was determined as 2.43 µg/mL and 1.13 µg/mL for ct -dsDNA and ct -ssDNA interaction, respectively. In the experiments, a low-cost electrode frequently used in electrochemical analysis, was preferred the pencil graphite electrode (PGE) was preferred. In the theoretical section, the chemical reactivity of 6-MP was highlighted in the light of Conceptual Density Functional Theory (CDFT) based reactivity descriptors and electronic structure principles. The nature of DNA-drug interaction was highlighted through Molecular Docking analysis and obtained docking results supported the experimental observations. Our study shows the interaction of 6-MP with DNA biosensors. It is an original study as it is being studied for the first time. Therefore, the results obtained will guide researchers in future studies on biosensors.

Highlighting the impact of blocking monolayers on DNA electrochemical sensors. Theoretical and experimental investigations under flow conditions

A model is proposed to account for the influence of electrode surface modifications in electrochemical DNA sensors operating under flow conditions. With blocking self-assembled monolayers of double-stranded DNA, the performance of the electrochemical transduction signal in the presence of a redox mediator is generally attributed to the rate of long-range electron transfer or to the screening effects of the monolayers due to negatively charged DNA. The originality of this model is here to only consider the influence of non-linear mass transport at the free-remaining sites. The model was tested for the detection of microRNAs (21 nucleotides) by implementing microchannel electrodes in the presence of an equimolar mixture of Fe(CN)63− / Fe(CN)64-. Two operating conditions leading to distinct monolayer structures were investigated using Pt and Au electrodes. The model successfully simulated the voltammograms confirming the apparent decrease in the signal transduction kinetics due to altered mass transport. These results were supported by measurements in electrochemical impedance spectroscopy.