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Halogen doped graphene quantum dots modulate TDP-43 phase separation and aggregation in the nucleus
Modulating amyloid protein phase separation and fibrilization may help in addressing neurodegenerative diseases. This study demonstrates that halogen-doped graphene quantum dots can modulate these processes in TDP-43 in both nucleus and cytoplasm.
- Hong Zhang
- , Huazhang Guo
- & Bin Dai
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Identifying regulators of aberrant stem cell and differentiation activity in colorectal cancer using a dual endogenous reporter system
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer. Here, authors develop a dual endogenous reporter system to identify functional regulators of aberrant stem cell and differentiation programs, showing that SMARCB1 restricts differentiation, and nominating other regulators with therapeutic potential.
- Sandor Spisak
- , David Chen
- & Nilay S. Sethi
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Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
G protein responses mediated by GPCRs may differ depending on their environment. Here, using highly sensitive Gi/o sensors, the authors reveal the specific pharmacological and Gi/o protein responses of some native GPCRs in neurons, and the influence of G protein composition.
- Chanjuan Xu
- , Yiwei Zhou
- & Jianfeng Liu
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Using the heme peroxidase APEX2 to probe intracellular H2O2 flux and diffusion
Previous genetically encoded H2O2 probes are based on reversible thiol oxidation. Here, a heme peroxidase is introduced as a thiol-independent H2O2 probe. APEX2 converts H2O2 into fluorescent or luminescent signals, allowing its quantification.
- Mohammad Eid
- , Uladzimir Barayeu
- & Tobias P. Dick
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Fluorogenic CRISPR for genomic DNA imaging
Conventional CRISPR-based approaches to monitor genomic loci can be hampered by high background and nonspecific nucleolar signal. Here, the authors propose a fluorogenic CRISPR (fCRISPR) tool that allows for high-contrast and sensitive imaging of genomic DNA.
- Zhongxuan Zhang
- , Xiaoxiao Rong
- & Xing Li
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Rapid and visual identification of β-lactamase subtypes for precision antibiotic therapy
The rapid identification of drug-resistant bacteria is vital for effective treatment and to avoid antibiotic misuse. Here authors report a paper-based sensor which utilises chromogenic carbapenem and cephalosporin substrates for the identification and discrimination of β-lactamase subtypes.
- Wenshuai Li
- , Jingqi Li
- & Dingbin Liu
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Single-sided magnetic resonance-based sensor for point-of-care evaluation of muscle
Magnetic resonance imaging is a useful clinical tool, but its widespread use is constrained by size, cost, and time. Here, the authors report the development of a magnetic resonance sensor for the clinical detection of muscle tissue, allowing for new point-of-care quantitative diagnostic measurements
- Sydney E. Sherman
- , Alexa S. Zammit
- & Michael J. Cima
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Blue-shift photoconversion of near-infrared fluorescent proteins for labeling and tracking in living cells and organisms
Photolabeling of intracellular molecules is an invaluable approach to study multiple cellular processes. Here, the authors report on the near-infrared to far-red photoconversion in the miRFP family of fluorescent proteins, which enables photolabeling entirely performed in the near-infrared range.
- Francesca Pennacchietti
- , Jonatan Alvelid
- & Ilaria Testa
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Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging
l-Lactate is increasingly recognized as a key metabolite and signalling molecule in mammals, but the methods to investigate it in vivo have been limited. Here, authors report a pair of improved biosensors—one green and one red—for visualizing l-lactate both inside and outside of cells.
- Yusuke Nasu
- , Abhi Aggarwal
- & Robert E. Campbell
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Repurposing conformational changes in ANL superfamily enzymes to rapidly generate biosensors for organic and amino acids
Biosensors have a wide number of potential applications, but rapidly constructing genetically encoded biosensors remains challenging. Here, authors report a method for rapidly converting ANL superfamily enzymes into biosensors for organic acids, based on their conformational changes upon binding.
- Jin Wang
- , Ning Xue
- & Meng Wang
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Widefield imaging of rapid pan-cortical voltage dynamics with an indicator evolved for one-photon microscopy
Genetically encoded voltage indicators need fast and large signals to allow widefield imaging of rapid neuronal activity. Here, the authors develop the indicator JEDI-1P and demonstrate pan-cortical voltage imaging and gamma-frequency tracking in awake mice in single trials.
- Xiaoyu Lu
- , Yunmiao Wang
- & François St-Pierre
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GLP-1R signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics
Agonists of the glucagon-like peptide-1 receptor are used to treat diabetes and obesity. Here, Wright et al. investigate the subcellular location of the receptor’s signaling events and uncover associations between signaling profiles and adverse drug reactions.
- Shane C. Wright
- , Aikaterini Motso
- & Volker M. Lauschke
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Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor
Genetically encoded dopamine sensors have emerged as an alternative to voltammetry for in vivo dopamine measurements. Here, the authors compare these two methods directly, and document dopamine responses during Pavlovian conditioning across the striatum.
- Armando G. Salinas
- , Jeong Oen Lee
- & David M. Lovinger
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Engineered NIR-II fluorophores with ultralong-distance molecular packing for high-contrast deep lesion identification
To achieve high-contrast in fluorescence imaging of deep tissues is challenging. Here, the authors develop NIR-II fluorescent small molecules with high brightness and emission extending to 1900 nm, enabling in vivo imaging of deep tissues with enhanced signal-to-background ratios.
- Zhe Feng
- , Yuanyuan Li
- & Jun Qian
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Phenotypically complex living materials containing engineered cyanobacteria
Engineered living materials (ELMs) are emerging as a field at the intersection of materials science and synthetic biology. Here, the authors describe a photosynthetic ELM composed of genetically engineered cyanobacteria in a hydrogel matrix, capable of bioremediation and inducible cell death.
- Debika Datta
- , Elliot L. Weiss
- & Jonathan K. Pokorski
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A genetically encoded sensor for visualizing leukotriene B4 gradients in vivo
Leukotriene B4 (LTB4) is a potent lipid chemoattractant driving leukocyte migration and neutrophil swarming, but methods for its real-time detection are lacking. Here, the authors develop GEM-LTB4, a genetically encoded fluorescent biosensor, and use it to visualize leukocyte-derived LTB4 gradients.
- Szimonetta Xénia Tamás
- , Benoit Thomas Roux
- & Balázs Enyedi
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Multidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor
The ability to independently control the expression of different genes is important for quantitative biology. Here, the authors report kinetic parameters, noise scaling, impact on growth, and the fundamental leakiness of a wide range of inducible transcriptional systems, including a new, highly light sensitive LOV-transcription factor.
- Vojislav Gligorovski
- , Ahmad Sadeghi
- & Sahand Jamal Rahi
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Ratiometric measurement of MAM Ca2+ dynamics using a modified CalfluxVTN
MAM Ca2+ dynamics play an important role in diverse biological processes, but directly and specifically measuring Ca2+ concentrations in this region is technically challenging. Here the authors report a MAM-specific BRET-based Ca2+ indicator called MAM-Calflux, which works as both a Ca2+ indicator and a structural marker due to its ratiometric nature.
- Eunbyul Cho
- , Youngsik Woo
- & Sang Ki Park
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N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics
Cysteine is a popular target of covalent drugs and can undergo redox modifications. Here, the authors developed cysteine probes, N-acryloylindole-alkynes, for imaging and chemoproteomics to study cysteine oxidation and to identify targetable hotspots by small molecule compounds.
- Tin-Yan Koo
- , Hinyuk Lai
- & Clive Yik-Sham Chung
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NERNST: a genetically-encoded ratiometric non-destructive sensing tool to estimate NADP(H) redox status in bacterial, plant and animal systems
NADP(H) is a crucial cofactor, acting as a reducing agent in numerous pathways in living organisms. Here the authors report a ratiometric biosensor named NERNST, which can be used to estimate the NADP(H) redox status in bacterial, plant and animal cells and organelles.
- Pamela E. Molinari
- , Adriana R. Krapp
- & Matias D. Zurbriggen
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A versatile bioelectronic interface programmed for hormone sensing
Ultrasensitive, real-time profiling of bio-analytes is a prerequisite for precision medicine. Here, the authors present a versatile bio-electronic interface (VIBE) to sense signaling cascade-guided receptor-ligand interactions and show that it can detect hormone levels in blood samples and differentiate individual metabolic conditions.
- Preetam Guha Ray
- , Debasis Maity
- & Martin Fussenegger
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A smart pathogen detector engineered from intracellular hydrogelation of DNA-decorated macrophages
Macrophages have the inherent capacity to recognise pathogenic microorganisms, highlighting their potential to be used in biosensing applications. Herein, the authors report a method to transform normally fragile macrophages into robust gelated cell particles for efficient bacterial capture and detection.
- Yueyue Gui
- , Yujing Zeng
- & Chao Li
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Specific, sensitive and quantitative protein detection by in-gel fluorescence
Recombinant proteins in complex solutions are typically detected with tag-specific antibodies in Western blots. Here, the author describes an antibody-free alternative in which tagged proteins are detected directly in polyacrylamide gels via fluorophore-labelling of the tagged protein using a ligase.
- Adrian C. D. Fuchs
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Quantifying PON1 on HDL with nanoparticle-gated electrokinetic membrane sensor for accurate cardiovascular risk assessment
Measuring proteomic subfractions of HDL can help during cardiovascular risk assessment. Here, the authors show, using a Nanoparticle-Gated Electrokinetic Membrane Sensor, the efficacy of Paroxonase 1 on HDL in its ability to diagnose cardiovascular disease compared to other commonly used methods.
- Sonu Kumar
- , Nalin Maniya
- & Hsueh-Chia Chang
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Differential sensing with arrays of de novo designed peptide assemblies
Differential sensing aims to mimic senses such as taste and smell through the use of synthetic receptors. Here, the authors show that arrays of de novo designed peptide assemblies can be used as sensor components to distinguish various analytes and complex mixtures.
- William M. Dawson
- , Kathryn L. Shelley
- & Derek N. Woolfson
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Pre-equilibrium biosensors as an approach towards rapid and continuous molecular measurements
Biosensors using ligand-receptor binding tend to operate under equilibrium conditions, but this can make real-time monitoring challenging. Here the authors provide a theoretical foundation for biosensing where ligand concentrations can be continuously measured without needing to reach equilibrium.
- Nicolò Maganzini
- , Ian Thompson
- & Hyongsok Tom Soh
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FRET-FISH probes chromatin compaction at individual genomic loci in single cells
Chromatin compaction affects many nuclear processes yet compaction levels at individual genomic loci have been notoriously difficult to assess. Here, Ana Mota and co-authors from the Bienko-Crosetto Lab present FRET-FISH for probing chromatin compaction at selected loci in single cells.
- Ana Mota
- , Szymon Berezicki
- & Magda Bienko
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A genetically encoded fluorescent biosensor for detecting itaconate with subcellular resolution in living macrophages
Itaconate has been identified as an immunomodulatory metabolite produced by activated macrophages, but methods for detecting itaconate in live cells are lacking. Here, the authors develop a fluorescent biosensor named BioITA for detecting itaconate in subcellular compartments of living macrophages.
- Pengkai Sun
- , Zhenxing Zhang
- & Xinjian Li
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Long-term monitoring of intravital biological processes using fluorescent protein-assisted NIR-II imaging
The retention time and toxicity of synthetic NIR-II fluorophores limit long-term application. Here the authors use infrared fluorescent proteins (iRFPs) as NIR-II probes for prolonged continuous imaging in mice, and generate a transgenic mouse model which they use to image liver and pancreas.
- Muxiong Chen
- , Zhe Feng
- & Zhengping Xu
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Flexible hyperspectral surface plasmon resonance microscopy
The authors developed a pristine hyperspectral SPR microscopy that enables monochromatic and polychromatic SPR imaging with flexible field-of-view option, single-pixel spectral SPR sensing and 2D quantification of thin films with resonant wavelength images.
- Ziwei Liu
- , Jingning Wu
- & Zhi-mei Qi
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Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor
β-TrCP plays an important role in diverse cellular processes such as the cell cycle and inflammation. Here the authors develop a biosensor for β-TrCP activity and use it to investigate β-TrCP dynamics during the cell cycle, and to screen a small-molecule library for β-TrCP activators and inhibitors.
- Debasish Paul
- , Stephen C. Kales
- & Steven D. Cappell
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Continuous biomarker monitoring with single molecule resolution by measuring free particle motion
Various applications would benefit from the ability to continuously measure biomolecules. Here the authors describe a biosensing technology based on the free diffusion of biofunctionalized particles hovering over a sensor surface, which enables monitoring of analytes (pM-µM) over long timespans.
- Alissa D. Buskermolen
- , Yu-Ting Lin
- & Menno W. J. Prins
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Resolving subcellular pH with a quantitative fluorescent lifetime biosensor
Measuring sub-cellular pH with high accuracy and spatiotemporal resolution remains challenging. Here, Johnston and co-workers develop a pH biosensor that combines the pH dependant fluorescent lifetime of mApple with deep learning to accurately determine sub-cellular pH in individual vesicles.
- Joshua J. Rennick
- , Cameron J. Nowell
- & Angus P. R. Johnston
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Location bias contributes to functionally selective responses of biased CXCR3 agonists
Subcellular signaling is critical to generating cellular responses that modulate inflammatory pathways at the chemokine receptor CXCR3. Eiger et al. determine that agonist-biased CXCR3 signaling at endosomes differs from that at the plasma membrane, proposing location bias as an important phenomenon in signal transduction.
- Dylan Scott Eiger
- , Noelia Boldizsar
- & Sudarshan Rajagopal
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Multiscale profiling of protease activity in cancer
The activity of multiple enzymes is dysregulated in cancer, but this cannot always be measured through enzyme expression. Here, the authors develop methods to measure protease activity across the organism, tissue, and single cell scales, and identify protease dysregulation in lung cancer and its response to targeted therapy.
- Ava P. Amini
- , Jesse D. Kirkpatrick
- & Sangeeta N. Bhatia
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β-arrestin1 and 2 exhibit distinct phosphorylation-dependent conformations when coupling to the same GPCR in living cells
Here the authors present improved intramolecular sensors for β-arrestin2 and 1, which enable assessment of conformational changes of both isoforms in living cells. These reveal that the same GPCR induces differential conformational rearrangements that determine the functional diversity between the two β-arrestins.
- Raphael S. Haider
- , Edda S. F. Matthees
- & Carsten Hoffmann
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Reaction-based fluorogenic probes for detecting protein cysteine oxidation in living cells
Fluorogenic detection of H2O2 in cells is established, but equivalent tools to monitor its cellular targets remain in their infancy. Here authors develop fluorogenic probes for detecting cysteine sulfenic acid, a redox modification inextricably linked to H2O2 signalling and oxidative stress.
- Renan B. Ferreira
- , Ling Fu
- & Kate S. Carroll
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A high-performance genetically encoded fluorescent indicator for in vivo cAMP imaging
The second messenger cAMP modulates a wide range of important biological processes. Here, the authors developed a fluorescent indicator termed G-Flamp1, which can accurately report levels of cAMP in living cells.
- Liang Wang
- , Chunling Wu
- & Jun Chu
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Photonic crystal enhanced fluorescence emission and blinking suppression for single quantum dot digital resolution biosensing
Nanoscale emitters are useful for measuring biomolecular interactions, but are limited by weak signals. Here, the authors use a photonic crystal surface for 3000-fold signal enhancement, achieving single emitter sensitivity with extended on-time, and demonstrate its application in miRNA biomarker sensing.
- Yanyu Xiong
- , Qinglan Huang
- & Brian T. Cunningham
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Defunctionalizing intracellular organelles such as mitochondria and peroxisomes with engineered phospholipase A/acyltransferases
Approaches for manipulating individual organelles are important for learning more about their functions. Here the authors report a tool utilising phospholipase A/acyltransferases (PLAATs) for rapid defunctionalisation of organelles through remodelling of the membrane phospholipids.
- Satoshi Watanabe
- , Yuta Nihongaki
- & Takanari Inoue
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Fatigue-free artificial ionic skin toughened by self-healable elastic nanomesh
Developing robust skin-like sensing materials is essential for soft electronics and robotics with extended service life. Here, inspired by the repairable nanofibrous structure of human skin, the authors engineer a fatigue-resistant artificial ionic skin toughened by self-healable elastic nanomesh.
- Jiqiang Wang
- , Baohu Wu
- & Peiyi Wu
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Article
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Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter
AMP activated protein kinase (AMPK) is a master regulator of cellular metabolism, but how AMPK activity is spatiotemporally regulated remains unclear. Here, Schmitt et al develop a sensitive biosensor for AMPK, which they use to uncover mechanisms for AMPK activity in the lysosome and nucleus.
- Danielle L. Schmitt
- , Stephanie D. Curtis
- & Jin Zhang
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Acceptor engineering for NIR-II dyes with high photochemical and biomedical performance
Small molecule NIR-II fluorophores are of interest for a range of applications but can suffer from chemical and photostability issues. Here, the authors report on the development of an acceptor molecule with improved stability in alkaline conditions expanding the range of possible applications.
- Aiyan Ji
- , Hongyue Lou
- & Zhen Cheng
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Porphyrin as a versatile visible-light-activatable organic/metal hybrid photoremovable protecting group
Photoremovable protecting groups (PPGs) represent one of the main contemporary implementations of photochemistry. Here, the authors show that meso-methylporphyrin unites traditionally exclusive features of organic and metal-complex PPGs within a single entity.
- Adiki Raja Sekhar
- , Youhei Chitose
- & Roy Weinstain
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Terahertz thermal curve analysis for label-free identification of pathogens
A label-free sensing method has been developed for identifying hazardous pathogens based on their intrinsic properties. This was possible by interrogating the temperature-dependent dielectric constant of the microbes in the far-infrared range.
- S. W. Jun
- & Y. H. Ahn
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A high-throughput multiparameter screen for accelerated development and optimization of soluble genetically encoded fluorescent biosensors
Fluorescent biosensors are important tools for studying cellular metabolism, but development and optimization are challenging. Koveal et al. present a high-throughput multiparameter screen for sensor performance, and used it to generate LiLac, a high-performance, quantitative lactate sensor.
- Dorothy Koveal
- , Paul C. Rosen
- & Gary Yellen
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Intelligent wireless theranostic contact lens for electrical sensing and regulation of intraocular pressure
Towards intelligent treatment for glaucoma, here authors demonstrate integrated wireless theranostic contact lenses for in situ electrical sensing of intraocular pressure and on demand anti-glaucoma drug delivery.
- Cheng Yang
- , Qianni Wu
- & Xi Xie
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Ratiometric afterglow luminescent nanoplatform enables reliable quantification and molecular imaging
Afterglow luminescence is promising for non-background molecular imaging in vivo. Here the authors report a ratiometric afterglow luminescent nanoplatform to generate activatable afterglow probes for quantification of specific analytes including NO.
- Yongchao Liu
- , Lili Teng
- & Weihong Tan
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Absolute measurement of cellular activities using photochromic single-fluorophore biosensors and intermittent quantification
Biosensors often report relative rather than absolute values. Here the authors report a method that utilises the photochromic properties of biosensors to provide an absolute measure of the analyte concentration or activity: photochromism-enabled absolute quantification (PEAQ) biosensing.
- Franziska Bierbuesse
- , Anaïs C. Bourges
- & Peter Dedecker
Rapid evolutionary change in trait correlations of single proteins