Nanoelectrochemistry reveals how soluble Aß42 oligomers alter vesicular storage and release of glutamate.

Glutamate (Glu) is the major excitatory transmitter in the nervous system. Impairment of its vesicular release by ß-amyloid (Aß) oligomers is thought to participate in pathological processes leading to Alzheimer's disease. However, it remains unclear whether soluble Aß42 oligomers affect intravesicular amounts of Glu or their release in the brain, or both. Measurements made in this work on single Glu varicosities with an amperometric nanowire Glu biosensor revealed that soluble Aß42 oligomers first caused a dramatic increase in vesicular Glu storage and stimulation-induced release, accompanied by a high level of parallel spontaneous exocytosis, ultimately resulting in the depletion of intravesicular Glu content and greatly reduced release. Molecular biology tools and mouse models of Aß amyloidosis have further established that the transient hyperexcitation observed during the primary pathological stage is mediated by an altered behavior of VGLUT1 responsible for transporting Glu into synaptic vesicles. Thereafter, an overexpression of Vps10p-tail-interactor-1a, a protein that maintains spontaneous release of neurotransmitters by selective interaction with t-SNAREs, resulted in a depletion of intravesicular Glu content, triggering advanced-stage neuronal malfunction. These findings are expected to open perspectives for remediating Aß42-induced neuronal hyperactivity and neuronal degeneration.

Microelectrochemical Sensor Reveals Tunneling Nanotube-Mediated Intercellular Communication of Endothelial Mechanotransduction.

The intercellular communication of mechanotransduction has a significant impact on various cellular processes. Tunneling nanotubes (TNTs) have been documented to possess the capability of transmitting mechanical stimulation between cells, thereby triggering an influx of Ca2+ ions. However, the related kinetic information on the TNT-mediated intercellular mechanotransduction communication is still poorly explored. Herein, we developed a classic and sensitive Pt-functionalized carbon fiber microelectrochemical sensor (Pt/CF) to study the intercellular communication of endothelial mechanotransduction through TNTs. The experimental findings demonstrate that the transmission of mechanical stimulation from stimulated human umbilical vein endothelial cells (HUVECs) to recipient HUVECs connected by TNTs occurred quickly (<100 ms) and effectively promoted nitric oxide (NO) production in the recipient HUVECs. The kinetic profile of NO release exhibited remarkable similarity in stimulated and recipient HUVECs. But the production of NO in the recipient cell is significantly attenuated (16.3%) compared to that in the stimulated cell, indicating a transfer efficiency of approximately 16.3% for TNTs. This study unveils insights into the TNT-mediated intercellular communication of mechanotransduction.

Microfluidic Electrochemical Integrated Sensor for Efficient and Sensitive Detection of Candida albicans.

Traditional methods for the detection of pathogenic bacteria are time-consuming, less efficient, and sensitive, which affects infection control and bungles illness. Therefore, developing a method to remedy these problems is very important in the clinic to diagnose the pathogenic diseases and guide the rational use of antibiotics. Here, microfluidic electrochemical integrated sensor (MEIS) has been investigated, functionally for rapid, efficient separation and sensitive detection of pathogenic bacteria. Three-dimensional macroporous PDMS and Au nanotube-based electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow separator" and "electrochemical detector," respectively. The 3D chaotic flow separator enhances the turbulence of the fluid, achieving an excellent bacteria capture efficiency. Meanwhile, the electrochemical detector provides a quantitative signal through enzyme-linked immunoelectrochemistry with improved sensitivity. The microfluidic electrochemical integrated sensor could successfully isolate Candida albicans (C. albicans) in the range of 30-3,000,000 CFU in the saliva matrix with over 95% capture efficiency and sensitively detect C. albicans in 1 h in oral saliva samples. The integrated device demonstrates great potential in the diagnosis of oral candidiasis and is also applicable in the detection of other pathogenic bacteria.

Electroactive polymer tag modified nanosensors for enhanced intracellular ATP detection.

ATP plays a crucial role in cell energy supply, so the quantification of intracellular ATP levels is particularly important for understanding many physio-pathological processes. The intracellular quantification of this non-electroactive molecule can be realized using aptamer-modified nanoelectrodes, but is hindered by the limited quantity of modification and electroactive tags on the nanosized electrodes. Herein, we developed a simple but effective electrochemical signal amplification strategy for intracellular ATP detection, which replaces the regular ATP aptamer-linked ferrocene monomer with a polymer, thus greatly magnifying the amounts of electrochemical reporters linked to one chain of the aptamer and enhancing the signals. This ferrocene polymer-ATP aptamer was further immobilized onto Au nanowire electrodes (SiC@C@Au NWEs) to achieve accurate quantification of intracellular ATP in single cells, presenting high electrochemical signal output and high specificity. This work not only provides a powerful tool for quantifying intracellular ATP but also offers a simple and versatile strategy for electrochemical signal amplification in the detection of broader non-electroactive molecules involved in different kinds of intracellular physiological processes.

Real-time monitoring of intracellular biochemical response in locally stretched single cell by a nanosensor.

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis.

Three-Dimensional Stretchable Sensor-Hydrogel Integrated Platform for Cardiomyocyte Culture and Mechanotransduction Monitoring.

Cardiomyocytes are responsible for generating contractile force to pump blood throughout the body and are very sensitive to mechanical forces and can initiate mechano-electric coupling and mechano-chemo-transduction. Remarkable progress has been made in constructing heart tissue by engineered three-dimensional (3D) culture models and in recording the electrical signals of cardiomyocytes. However, it remains a severe challenge for real-time acquiring of the transient biochemical information in cardiomyocyte mechano-chemo-transduction. Herein, we reported a multifunctional platform by integrating a 3D stretchable electrochemical sensor with collagen hydrogel for the culture, electrical stimulation, and electrochemical monitoring of cardiomyocytes. The 3D stretchable electrochemical sensor was prepared by assembling functionalized conductive polymer PEDOT:PSS on an elastic scaffold, which showed excellent electrochemical sensing performance and stability under mechanical deformations. The integration of a 3D stretchable electrochemical sensor with collagen hydrogel provided an in vivo-like microenvironment for cardiomyocyte culture and promoted cell orientation via in situ electrical stimulation. Furthermore, this multifunctional platform allowed real-time monitoring of stretch-induced H2O2 release from cardiomyocytes under their normal and pathological conditions, as well as pharmacological interventions.

Biotransformation of the saponins in Panax notoginseng leaves mediated by gut microbiota from insomniac patients.

Saponins extracted from Panax notoginseng leaves by methanol or water could be orally administrated for insomnia with very low bioavailability, which might be bio-converted by gut microbiota to generate potential bioactive products. Moreover, gut microbiota profiles from insomniac patients are very different from healthy subjects. We aimed to compare the metabolic characteristics and profiles of the two saponins extract by incubation with gut microbiota from insomniac patients. The ginsenosides, notoginsenosides, and metabolites were identified and relatively quantified by high-performance liquid chromatography-tandem mass spectrometry. Gut microbiota was profiled by 16S ribosomal RNA gene sequencing. The results showed that saponins were very different between methanol or water extract groups, which were metabolized by gut microbiota to generate similar yields. The main metabolites included ginsenoside Rd, ginsenoside F2 , ginsenoside C-Mc or ginsenoside C-Y, ginsenoside C-Mx, ginsenoside compound K, and protopanaxadiol in both groups, while gypenoside XVII, notoginsenoside Fe, ginsenoside Rd2 , and notoginsenoside Fd were the intermediates in the methanol group. Moreover, the microbial, Faecalibacterium prausnitzi, could bio-convert the saponins to obtain the corresponding metabolites. Our study implied that saponins extracted from P. notoginseng leaves by methanol or water could be used for insomniac patients due to gut microbiota biotransformation.

Detection of Unfolded Cellular Proteins Using Nanochannel Arrays with Probe-Functionalized Outer Surfaces.

Nanochannel technology has emerged as a powerful tool for label-free and highly sensitive detection of protein folding/unfolding status. However, utilizing the inner walls of a nanochannel array may cause multiple events even for proteins with the same conformation, posing challenges for accurate identification. Herein, we present a platform to detect unfolded proteins through electrical and optical signals using nanochannel arrays with outer-surface probes. The detection principle relies on the specific binding between the maleimide groups in outer-surface probes and the protein cysteine thiols that induce changes in the ionic current and fluorescence intensity responses of the nanochannel array. By taking advantage of this mechanism, the platform has the ability to differentiate folded and unfolded state of proteins based on the exposure of a single cysteine thiol group. The integration of these two signals enhances the reliability and sensitivity of the identification of unfolded protein states and enables the distinction between normal cells and Huntington's disease mutant cells. This study provides an effective approach for the precise analysis of proteins with distinct conformations and holds promise for facilitating the diagnoses of protein conformation-related diseases.

Fast Antioxidation Kinetics of Glutathione Intracellularly Monitored by a Dual-Wire Nanosensor.

The glutathione (GSH) system is one of the most powerful intracellular antioxidant systems for the elimination of reactive oxygen species (ROS) and maintaining cellular redox homeostasis. However, the rapid kinetics information (at the millisecond to the second level) during the dynamic antioxidation process of the GSH system remains unclear. As such, we specifically developed a novel dual-wire nanosensor (DWNS) that can selectively and synchronously measure the levels of GSH and ROS with high temporal resolution, and applied it to monitor the transient ROS generation as well as the rapid antioxidation process of the GSH system in individual cancer cells. These measurements revealed that the glutathione peroxidase (GPx) in the GSH system is rapidly initiated against ROS burst in a sub-second time scale, but the elimination process is short-lived, ending after a few seconds, while some ROS are still present in the cells. This study is expected to open new perspectives for understanding the GSH antioxidant system and studying some redox imbalance-related physiological.

Homeostasis inside Single Activated Phagolysosomes: Quantitative and Selective Measurements of Submillisecond Dynamics of Reactive Oxygen and Nitrogen Species Production with a Nanoelectrochemical Sensor.

Reactive oxygen and nitrogen species (ROS/RNS) are generated by macrophages inside their phagolysosomes. This production is essential for phagocytosis of damaged cells and pathogens, i.e., protecting the organism and maintaining immune homeostasis. The ability to quantitatively and individually monitor the four primary ROS/RNS (ONOO-, H2O2, NO, and NO2-) with submillisecond resolution is clearly warranted to elucidate the still unclear mechanisms of their rapid generation and to track their concentration variations over time inside phagolysosomes, in particular, to document the origin of ROS/RNS homeostasis during phagocytosis. A novel nanowire electrode has been specifically developed for this purpose. It consisted of wrapping a SiC nanowire with a mat of 3 nm platinum nanoparticles whose high electrocatalytic performances allow the characterization and individual measurements of each of the four primary ROS/RNS. This allowed, for the first time, a quantitative, selective, and statistically robust determination of the individual amounts of ROS/RNS present in single dormant phagolysosomes. Additionally, the submillisecond resolution of the nanosensor allowed confirmation and measurement of the rapid ability of phagolysosomes to differentially mobilize their enzyme pools of NADPH oxidases and inducible nitric oxide synthases to finely regulate their homeostasis. This reveals an essential key to immune responses and immunotherapies and rationalizes its biomolecular origin.

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma.

BACKGROUND: Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. METHODS: We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. RESULTS: Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10- 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). CONCLUSIONS: Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. TRIAL REGISTRATION: Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

Redox Homeostasis Alteration in Endothelial Mechanotransduction Monitored by Dual Stretchable Electrochemical Sensors.

In vivo, endothelial cells are permanently subjected to dynamic cyclic stretch and adapt to it through the release of vasoactive substances. Among them, reactive oxygen species (ROS) and nitric oxide (NO) are indispensable redox molecules, the contents of which and their ratio are closely implicated with endothelial redox homeostasis. However, simultaneous and quantitative monitoring of ROS and NO release in endothelial mechanotransduction remains a great challenge. Herein, a stretchable electrochemical device is developed with a dual electrode based on gold nanotubes decorated with uniform and tiny platinum nanoparticles. This hybrid nanostructure endows the sensor with high sensitivity toward both hydrogen peroxide (H2O2) (as the most stable ROS) and NO electrooxidation. Importantly, the two species can be well discriminated by applying different potentials, which allows simultaneous monitoring of H2O2 and NO release in stretch-induced endothelial mechanotransduction by the same device. The results of quantitative analysis suggest that endothelial redox homeostasis and its alteration are strongly related to vascular biomechanical and biochemical milieus. Further investigation reveals that the interplay of ROS and NO signaling has an important role in the regulation of endothelial redox state. This work will greatly facilitate the deep understanding of the molecular mechanism of endothelial dysfunction and vascular disorder.

Versatile Construction of Biomimetic Nanosensors for Electrochemical Monitoring of Intracellular Glutathione.

The current strategies for nanoelectrode functionalization usually involve sophisticated modification procedures, uncontrollable and unstable modifier assembly, as well as a limited variety of modifiers. To address this issue, we propose a versatile strategy for large-scale synthesis of biomimetic molecular catalysts (BMCs) modified nanowires (NWs) to construct functionalized electrochemical nanosensors. This design protocol employs an easy, controllable and stable assembly of diverse BMCs-poly(3,4-ethylenedioxythiophene) (PEDOT) composites on conductive NWs. The intrinsic catalytic activity of BMCs combined with outstanding electron transfer ability of conductive polymer enables the nanosensors to sensitively and selectively detect various biomolecules. Further application of sulfonated cobalt phthalocyanine functionalized nanosensors achieves real-time electrochemical monitoring of intracellular glutathione levels and its redox homeostasis in single living cells for the first time.

Soft Electrodes for Electrochemical and Electrophysiological Monitoring of Beating Cardiomyocytes.

Many cells in vivo have their inherent motions, which involve numerous biochemical and biophysical signals synergistically regulating cell behavior and function. However, existing methods offer little information about the concurrently chemical and physical responses of dynamically pulsing cells. Here, we report a soft electrode with an electrospun poly(3,4-ethylenedioxythiophene) (PEDOT)-based nanomesh to fully comply with spontaneous motions of cells. Moreover, this electrode demonstrated excellent electrical conductivity, electrochemical performance and cellular biocompatibility. Cardiomyocytes cultured thereon exhibited autonomous and rhythmic contractility, and synchronously induced mechanical deformation of the underlying electrode, which allowed real-time monitoring of nitric oxide release and electrophysiological activity of cardiomyocytes. This work provides a promising way toward recording chemical and electrical signals of biological systems with their natural motions.

A Three-Dimensional Electrochemical Biosensor Integrated with Hydrogel Enables Real-Time Monitoring of Cells under Their In Vivo-like Microenvironment.

Three-dimensional (3D) cell culture can better reproduce the in vivo cell environment and has been extensively used in fields such as tissue engineering, drug screening, and pathological research. Despite the tremendous advancement of 3D cultures, an analysis technique that could collect real-time information of the biological processes therein is sorely lacking. Electrochemical sensing with fast response and high sensitivity has played a vital role in real-time monitoring of living cells, but most current sensors are based on planar electrodes and fail to perfectly match the 3D cell culture matrix. Herein, we developed a robust 3D electrochemical sensor based on functionalized graphene foam (GF), which could be integrated with hydrogels for the 3D culture and in situ monitoring of cells for the first time. Specifically, platinum nanoparticles (Pt NPs) electrodeposited on GF (GF/Pt NPs) conferred the prominent electrochemical sensing performance, and the anti-fouling coating of poly(3,4-ethylenedioxythiophene) (PEDOT) endowed the GF/Pt NPs electrode with greatly improved stability. As a proof of concept, collagen hydrogel with microglia seeded in was filled into the interspace of the 3D GF/Pt NPs/PEDOT sensor to establish an integrated platform, which allowed the successful real-time monitoring of reactive oxygen species released from microglia in the collagen matrix. Given the versatility, our proposed biosensor in conjunction with various 3D culture models will serve as an excellent tool to provide biochemical information of cells under their in vivo-like microenvironment.

Chemical Tagging Assisted Mass Spectrometry Analysis Enables Sensitive Determination of Phosphorylated Compounds in a Single Cell.

Polar phosphorylated metabolites are involved in a variety of biological processes and play vital roles in energetic metabolism, cofactor regeneration, and nucleic acid synthesis. However, it is often challenging to interrogate polar phosphorylated metabolites and compounds from biological samples. Liquid chromatography-mass spectrometry (LC/MS) now plays a central role in metabolomic studies. However, LC/MS-based approaches have been hampered by the issues of the low ionization efficiencies, low in vivo concentrations, and less chemical stability of polar phosphorylated metabolites. In this work, we synthesized paired reagents of light and heavy isotopomers, 2-(diazomethyl)phenyl)(9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)methanone (DMPI) and d3-(2-(diazomethyl)phenyl)(9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)methanone (d3-DMPI). The paired reagents of DMPI and d3-DMPI carry diazo groups that can efficiently and selectively react with the phosphate group on polar phosphorylated metabolites under mild conditions. As a proof of concept, we found that the transfer of the indole heterocycle group from DMPI/d3-DMPI to ribonucleotides led to the significant increase of ionization efficiencies of ribonucleotides during LC/MS analysis. The detection sensitivities of these ribonucleotides increased by 25-1137-fold upon DMPI tagging with the limits of detection (LODs) being between 7 and 150 amol. With the developed method, we achieved the determination of all the 12 ribonucleotides from a single mammalian cell and from a single stamen of Arabidopsis thaliana. The method provides a valuable tool to investigate the dynamic changes of polar phosphorylated metabolites in a single cell under particular conditions.

A Three-Dimensional Conductive Scaffold Microchip for Effective Capture and Recovery of Circulating Tumor Cells with High Purity.

Effective acquirement of highly pure circulating tumor cells (CTCs) is very important for CTC-related research. However, it is a great challenge since abundant white blood cells (WBCs) are always co-collected with CTCs because of nonspecific bonding or low depletion rate of WBCs in various CTC isolation platforms. Herein, we designed a three-dimensional (3D) conductive scaffold microchip for highly effective capture and electrochemical release of CTCs with high purity. The conductive 3D scaffold was prepared by dense immobilization of gold nanotubes (Au NTs) on porous polydimethylsiloxane and was functionalized with a CTC-specific biomolecule facilitated by a Au-S bond before embedding into a microfluidic device. The spatially distributed 3D macroporous structure compelled cells to change migration from linear to chaotic and the densely covered Au NTs enhanced the topographic interaction between cells and the substrate, thus synergistically improving the CTC capture efficiency. The Au NT-coated 3D scaffold had good electrical conductivity and the Au-S bond was breakable by voltage exposure so that captured CTCs could be specifically released by electrochemical stimulation while nonspecifically bonded WBCs were not responsive to this process, facilitating recovery of CTCs with high purity. The 3D conductive scaffold microchip was successfully applied to obtain highly pure CTCs from cancer patients' blood, benefiting the downstream analysis of CTCs.

Falcarindiol and dichloromethane fraction are bioactive components in Oplopanax elatus: Colorectal cancer chemoprevention via induction of apoptosis and G2/M cell cycle arrest mediated by cyclin A upregulation.

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

Stretchable Electrochemical Sensors for Cell and Tissue Detection.

Electrochemical sensing based on conventional rigid electrodes has great restrictions for characterizing biomolecules in deformed cells or soft tissues. The recent emergence of stretchable sensors allows electrodes to conformally contact to curved surfaces and perfectly comply with the deformation of living cells and tissues. This provides a powerful strategy to monitor biomolecules from mechanically deformed cells, tissues, and organisms in real time, and opens up new opportunities to explore the mechanotransduction process. In this minireview, we first summarize the fabrication of stretchable electrodes with emphasis on the nanomaterial-enabled strategies. We then describe representative applications of stretchable sensors in the real-time monitoring of mechanically sensitive cells and tissues. Finally, we present the future possibilities and challenges of stretchable electrochemical sensing in cell, tissue, and in vivo detection.