High-viscosity Environments Research Articles

Direct observation of the twisted intramolecular charge-transfer state in polycyclic purinium salts.

Based on femtosecond transient absorption spectroscopy (fs-TAS) of 3-methyl-7,8-diphenyl-3H-purino[6,1-a] isoquinolin-6-ium trifluoromethanesulfonate in dimethyl sulfoxide (DMSO), the stimulated emission (SE) signal redshifts from 400 to 500 nm in 4.8 ps. In a glycerol/DMSO mixed solution, when the glycerol content is 25% and 50%, the delay is extended to 6.9 and 68 ps, respectively. The theoretical emission spectrum in the scanning of potential energy curves demonstrates that the rotation of the φ2 with a lower energy barrier (16.1 kcal/mol) occurs prior to that of φ1. In addition, the purinium salt molecule has a twisted intramolecular charge transfer (TICT) process occurring from the locally excited (LE) state to the charge transfer (CT) state, and torsion of φ2 is restrained in high-viscosity environments, which induces the redshift of SE and its increasing lifetime.

A dual-responsive fluorescent probe for cellular hypoxia and tumor imaging based on nitroreductase and viscosity synergy

Nitroreductase (NTR), an enzyme that operates within the cytoplasm, relies on flavin mononucleotide or flavin adenine dinucleotide for its activity. In tumor cells, hypoxic conditions often lead to an increase in NTR levels. Consequently, the development of fluorescent probes capable of detecting NTR activity is crucial for the monitoring of hypoxia in biological systems. This study presents the one-step synthesis of a near-infrared fluorescent probe, DSM-NO2. The probe was highly sensitive to NTR and caused a fluorescence enhancement by 50-fold, with a detection limit as low as 1 ng/mL. Under hypoxic conditions in tumor cells, not only does NTR increase, but the cellular viscosity also rises. In high-viscosity environments, the fluorescence enhancement could reach up to 220-fold, and the detection limit could be further reduced to 55 pg/mL. The reaction mechanism was thoroughly investigated using mass spectrometry, molecular docking, and theoretical calculations. Moreover, the probe was successfully applied in the real-time monitoring and visualization analysis of NTR during the growth of Escherichia coli and in the hypoxic state of cancer cells. Additionally, through nebulized inhalation, the probe was successfully employed for in situ fluorescent imaging studies in a murine model of lung cancer.

High-fidelity imaging of drug-induced acute gastritis by using a fluorescent and photoacoustic dual-modal probe with good stability in stomach acid

In consideration of deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-modal probes are much more desirable. However, dual-modal imaging of gastritis using molecular probes remains a challenge due to the harsh gastric acid environment in the stomach. Based on the positive correlation between gastritis and cell viscosity, stomach acid-stable and viscosity-activated probes could potentially diagnose gastritis. As a proof of concept, herein, a fluorescent and photoacoustic dual-modal probe (named WSP-1) is revealed for the imaging of drug-induced acute gastritis in vivo. WSP-1 exhibits viscosity-dependent fluorescence emission and photoacoustic signals. A rotatable C–C single bond is incorporated into the D-π-A structure of WSP-1, which could facilitate the formation of the twisted intramolecular charge transfer (TICT) state in a low-viscosity environment (weak fluorescence/PA signal) and the intramolecular charge transfer (ICT) state in a high-viscosity environment (strong fluorescence/PA signal). WSP-1 has demonstrated the capability to target mitochondria and can be utilized to monitor the viscosity enhancement of cells during inflammation. Most importantly, WSP-1 exhibits good optical and structural stability in gastric acid. By leveraging these desirable features of WSP-1, we have achieved fluorescent and 3D photoacoustic in situ imaging of drug-induced acute gastritis following oral administration of WSP-1.

Viscosity-dependent swimming patterns assist Aliivibrio fischeri for symbiont partner finding

Bacteria employ diverse swimming patterns for chemotaxis, influenced by factors including flagellar arrangements, motor rotation, flagellar filament configurations, and polymorphism. Understanding the chemotactic strategy of in locating a squid partner is paramount for comprehending this highly species-specific symbiosis. In this study, we applied three-dimensional swimming tracking and real-time visualization of lophotrichous flagellar configurations. These techniques unveiled viscosity-dependent transitions in swimming patterns, shifting from push-pull to push-wrap modes. Notably, our research also revealed coupled flagellar switching and polymorphic transformations during the wrap mode, significantly extending 's backward swimming duration and, consequently, its overall runtime. This strategic adaptation allows to broaden its effective search range, particularly within high-viscosity environments like the squid light organ. In response to attractants, the coupling rate is reduced to facilitate efficient short-range searching. These innovative chemotactic strategies ensure precise navigation for in locating and colonizing its symbiotic partner, the squid . Published by the American Physical Society 2024

High-fidelity imaging of fatty liver in vivo with a fluorescent and photoacoustic dual-mode probe by taking advantage of the liver “first pass effect”

Intravenous injection is the most commonly used method for probe delivery in bio-imaging. While, the oral administration method might be more efficient than intravenous injection for fatty liver imaging due to the existence of liver “first pass effect”. However, this fundamental question has not yet been clarified. Meanwhile, in consideration of the deep tissue imaging and signal fidelity, fluorescent-photoacoustic (PA) dual-mode probes are much more desirable. Herein, an orally administrable dual-mode probe WSP-3 is revealed as a tool for imaging of the fatty liver disease and providing an insight into the above scientific question. A D-π-A system is linked with a rotatable CC single bond in WSP-3, which facilitates the formation of a TICT state in low viscosity environments and an ICT state in high viscosity environments. Base on the positive correlation between fatty liver disease and cell viscosity, dual-mode imaging of non-alcoholic fatty liver disease (NAFLD) and drug-induced fatty liver disease (DIFLD) in vivo was accomplished. Moreover, control experiments indicated that the oral administration method demonstrated higher efficiency in fatty liver disease imaging, providing a fundamental reference for further probe-based fatty liver imaging.

A dual-emission fluorescent probe with independent polarity and viscosity responses: The synthesis, spectroscopy and bio-imaging applications

Viscosity and polarity are essential parameters that play critical roles in various physiological processes. Thus, dual-emission fluorescent probes that respond to both polarity and viscosity are highly sought-after tools for studying these processes. In addressing this need, a novel fluorescent probe (L), with dual emissions centered at 460 nm and 780 nm, which can sensitively respond to polarity and viscosity respectively, has been developed. Probe (L) is constructed through rational molecular design, utilizing two conjugated synthons connected by a π-bond to form a D-π-A system. The twisted intramolecular charge transfer (TICT) state is dominant in low-viscosity environments, resulting in weak near-infrared (NIR) fluorescence. Conversely, the intramolecular charge transfer (ICT) state is expected to prevail in high-viscosity environments, leading to strong NIR fluorescence. The polarity-sensitive fluorescence centered at 460 nm can be attributed to the emission of the coumarin unit. Moreover, probe (L) exhibits low cytotoxicity and primarily targets mitochondria. By leveraging the dual-emission properties of probe (L), real-time imaging of polarity and viscosity fluctuations within cells has been achieved. Additionally, probe (L) can be used for in situ and in vivo imaging of rheumatoid arthritis (RA) with good imaging resolution.

Construction of a Near-Infrared Fluorescent Probe for Dynamic Monitoring and Early Diagnosis of Heart Failure.

Cardiac hypertrophy characterized by abnormal cardiomyocyte viscosity is a typical sign of heart failure (HF) with vital importance for early diagnosis. However, current biochemical and imaging diagnostic methods are unable to detect this subclinical manifestation. In this work, we developed a series of NIR-I fluorescence probes for detecting myocardial viscosity based on the pyridazinone scaffold. The probes showed weak fluorescence due to free intramolecular rotation under low-viscosity conditions, while they displayed strong fluorescence with limited intramolecular rotation in response to a high-viscosity environment. Among them, CarVis2 exhibited higher stability and photobleaching resistance than commercial dyes. Its specific response to viscosity was not influenced by the pH and biological species. Furthermore, CarVis2 showed rapid and accurate responses to the viscosity of isoproterenol (ISO)-treated H9C2 cardiomyocytes with good biocompatibility. More importantly, CarVis2 demonstrated excellent sensitivity in monitoring myocardial viscosity variation in HF mice in vivo, potentially enabling earlier noninvasive identification of myocardial abnormalities compared to traditional clinical imaging and biomarkers. These findings revealed that CarVis2 can serve as a powerful tool to monitor myocardial viscosity, providing the potential to advance insights into a pathophysiological mechanism and offering a new reference strategy for early visual diagnosis of HF.

Technical transformation of heavy/ultra-heavy oil production in China driven by low carbon goals: A review

With the growing global energy demand and limited production of conventional crude oil, the extraction of unconventional heavy and extra-heavy oil is receiving unprecedented attention. China is the fourth largest producer of heavy oil. High viscosity and complex formation environments increase the difficulty of exploiting heavy oil. To alleviate the economic cost and environmental pollution pressure brought by heavy oil production, China has achieved significant advancement in the innovation of heavy oil recovery, including accelerating the transformation of thermal technology to non-thermal technology and the use of new energy technology to achieve the goal of low-carbon economy and green environmental protection. Based on the background of heavy oil in China, this paper recharacterizes the high-viscosity mechanism of heavy oil. From different aspects, including basic principles, main characteristics, applicability, limitations, and challenges, this paper comprehensively reviews existing heavy oil recovery technologies, including thermal recovery, in-situ upgrading, cold recovery, and new energy technologies.Currently, in China, the main target of heavy oil recovery is achieving the “carbon peaking and carbon neutrality” goals, which can be described as low energy consumption, low emission, and low pollution. To facilitate the low-carbon transition in the extraction of heavy/extra-heavy oil and attain environmental sustainability goals, it is essential to increase the proportion of non-thermal factors in thermal recovery technologies, develop efficient in-situ catalysts, adopt clean cold extraction techniques, and advance the development of new energy technologies.

A triphenylamine-thiophene-based fluorescent probe for the dual-channel detection and imaging of hypochlorite and viscosity in live cells

In this research, a new triphenylamine-thiophene-based fluorescent probe, denoted as TTD, was constructed for simultaneous detection of viscosity and hypochlorite (ClO−) with dual-response signals. The hindrance of intramolecular bond rotation within TTD in a high-viscosity environment turns on the probe’s emission at 600 nm, resulting in strong red fluorescence. Simultaneously, the oxidation of the imine moiety to the aldehyde product, induced by ClO−, leads to substantial emission enhancement at 460 nm, generating vivid blue fluorescence. As a result, TTD can be employed for the dual-color visualization of changes in viscosity and ClO− levels, demonstrating good selectivity. TTD has been applied to image the elevated level of viscosity induced by nystatin, rotenone or erastin as well as exogenously introduced ClO− in living cells. Importantly, from two independent emission channels, TTD is capable of monitoring both ClO− and viscosity fluctuations within live cells during the inflammatory response triggered by lipopolysaccharide (LPS).

Near-infrared fluorescent probe based on carboxylesterase 2 and viscosity cascade response for early diagnosis of thyroid cancer

Carboxylesterase 2 (CES2) plays a critical role in the metabolism of ester- and amide-containing drugs and thus has an impact on drug efficacy and toxicity. This study introduces QVJ-CES2, a near-infrared fluorescent probe designed to enhance thyroid cancer diagnosis through CES2 enzyme activity and distinct cellular viscosity of thyroid cells. The probe's dual-response mechanism significantly amplified fluorescence in high-viscosity environments, thus had high sensitivity. Our findings revealed that QVJ-CES2 could detect CES2 activity with a limit of detection as low as 1.9 ng/mL. In vitro experiments confirmed the rapid and selective response of QVJ-CES2 to CES2 and the ability to distinguish cancer cells from their normal cells with high specificity. Most importantly, the fluorescence intensity difference between cancerous and normal cells after incubation with the probe was as high as 7-fold, attributable to the synergistic enzyme and viscosity cascade response. Further, in vivo studies demonstrated that the probe was effective in accurately identifying thyroid cancer tissues, showing that it is a promising tool for early cancer detection and precise surgical interventions.

Computational Approaches to Predict Protein-Protein Interactions in Crowded Cellular Environments.

Investigating protein-protein interactions is crucial for understanding cellular biological processes because proteins often function within molecular complexes rather than in isolation. While experimental and computational methods have provided valuable insights into these interactions, they often overlook a critical factor: the crowded cellular environment. This environment significantly impacts protein behavior, including structural stability, diffusion, and ultimately the nature of binding. In this review, we discuss theoretical and computational approaches that allow the modeling of biological systems to guide and complement experiments and can thus significantly advance the investigation, and possibly the predictions, of protein-protein interactions in the crowded environment of cell cytoplasm. We explore topics such as statistical mechanics for lattice simulations, hydrodynamic interactions, diffusion processes in high-viscosity environments, and several methods based on molecular dynamics simulations. By synergistically leveraging methods from biophysics and computational biology, we review the state of the art of computational methods to study the impact of molecular crowding on protein-protein interactions and discuss its potential revolutionizing effects on the characterization of the human interactome.

Effect of polymethyl methacrylate on in situ patterning of perovskite quantum dots by inkjet printing.

The preparation of perovskite quantum dots (PQDs) using an in situ inkjet printing method is beneficial for improving the problems of aggregation and photoluminescence (PL) quenching during long-term storage. However, the stability of PQDs prepared using this method is still not ideal, and the morphology of in situ-printed patterns needs to be optimized. To address these problems, this study introduced polymethyl methacrylate (PMMA) into the process of in situ inkjet printing of PQDs and explored the effect of PMMA on the in situ patterning effect of PQDs. The results showed that using a mixed precursor solution containing a small amount of PMMA as the printing ink can slow down the shrinkage process of ink droplets and improve the uniformity of film formation. As the printing substrate, PMMA provided a suitable high-viscosity environment for the in situ growth of PQDs. This could effectively suppress the coffee ring effect. In addition, the interaction between the C=O=C group in PMMA and metal ion Pb2+ in the CsPbBr3 precursor molecules was favourable to enhancing the density of PQDs. The prepared PMMA-coated CsPbBr3 quantum dots (QDs) pattern had high stability and could maintain at 90.08% PL intensity after 1 week of exposure to air.

Viscosity-dependent determinants of Campylobacter jejuni impacting the velocity of flagellar motility.

Bacteria can adapt flagellar motor output in response to the load that the extracellular milieu imparts on the flagellar filament to enable propulsion. Bacteria can adapt flagellar motor output in response to the load that the extracellular milieu imparts on the flagellar filament to enable propulsion through diverse environments. These changes may involve increasing power and torque in high-viscosity environments or reducing power and flagellar rotation upon contact with a surface. C. jejuni swimming velocity in low-viscosity environments is comparable to other bacterial flagellates and increases significantly as external viscosity increases. In this work, we provide evidence that the mechanics of the C. jejuni flagellar motor has evolved to naturally promote high swimming velocity in high-viscosity environments. We found that C. jejuni produces VidA and VidB as auxiliary proteins to specifically affect flagellar motor activity in low viscosity to reduce swimming velocity. Our findings provide some of the first insights into different mechanisms that exist in bacteria to alter the mechanics of a flagellar motor, depending on the viscosity of extracellular environments.

Synthesis and properties of D-π-A triphenylamine derivatives with solvatochromism and bioimaging application

D-π-A type molecular structures often exhibit excellent photophysical properties due to intramolecular charge-transfer interactions. Herein, two donor-π-acceptor (D-π-A) type triphenylamine derivatives were designed and synthesized. These two compounds exhibited bright solid-state emission with orange-red fluorescence (compound 1, 620 nm) and near-infrared (NIR) fluorescence (compound 2, 650 nm). Moreover, the photophysical properties studies showed that these two compounds exhibited significant solvatochromism with different solvent polarity, indicating their effective intramolecular charge transfer. Furthermore, the two compounds showed remarkable aggregation-induced emission (AIE) effect, and compound 2 was more likely to form the aggregation state in the presence of less water. In addition, compared to compound 1, compound 2 only had a more sensitive response to high viscosity environments. These results indicate that the additional phenyl ring could be an alternative way to tune the fluorescence behaviors and provide a new strategy to design AIE-active and solvatochromism dyes. Finally, cell imaging experiments showed that these two compounds had the ability to be applied for bioimaging in living cells.

A viscosity-sensitivity probe for cross-platform multimodal imaging from mitochondria to animal

Viscosity in biological systems is a critical factor for various physiological process, including signal transduction and metabolisms of substance and energy. Abnormal viscosity has been proven as a key feature of many diseases, thereby real-time monitoring of viscosities in cells and in vivo is of great significance for the diagnosis and therapy of related diseases. Up to date, it is still challenging to monitor viscosity cross-platform from organelles to cells to animals with a single probe. Here, we report a benzothiazolium-xanthene probe with rotatable bonds that switch on the optical signals in high viscosity environment. The enhancements of absorption, fluorescence intensity and lifetime signals allow to dynamically monitoring the viscosity change in mitochondria and cells, while near infrared absorption and emission facilitate imaging the viscosity with both fluorescence and photoacoustic imaging in animals. The cross-platform strategy is capable of monitoring the microenvironment with multifunctional imaging across various levels.

Viscous Microcapsules as Microbioreactors to Study Mesenchymal Stem/Stromal Cells Osteolineage Commitment.

It is essential to design a multifunctional well-controlled platform to transfer mechanical cues to the cells in different magnitudes. This study introduces a platform, a miniaturized bioreactor, which enables to study the effect of shear stress in microsized compartmentalized structures. In this system, the well-established cell encapsulation system of liquefied capsules (LCs) is used as microbioreactors in which the encapsulated cells are exposed to variable core viscosities to experience different mechanical forces under a 3D dynamic culture. The LC technology is joined with electrospraying to produce such microbioreactors at high rates, thus allowing the application of microcapsules for high-throughput screening. Using this platform for osteogenic differentiation as an example, shows that microbioreactors with higher core viscosity which produce higher shear stress lead to significantly higher osteogenic characteristics. Moreover, in this system the forces experienced by cells in each LC are simulated by computational modeling. The maximum wall shear stress applied to the cells inside the bioreactor with low, and high core viscosity environment is estimated to be 297 and 1367 mPa, respectively, for the experimental setup employed. This work outlines the potential of LC microbioreactors as a reliable in vitro customizable platform with a wide range of applications.

Fluorescent Molecular Rotors Based on Hinged Anthracene Carboxyimides.

Temperature and viscosity are essential parameters in medicine, environmental science, smart materials, and biology. However, few fluorescent sensor publications mention the direct relationship between temperature and viscosity. Three anthracene carboxyimide-based fluorescent molecular rotors, 1DiAC∙Cl, 2DiAC∙Cl, and 9DiAC∙Cl, were designed and synthesized. Their photophysical properties were studied in various solvents, such as N, N-dimethylacetamide, N, N-dimethylformamide, 1-propanol, ethanol, dimethyl sulfoxide, methanol, and water. Solvent polarizability resulted in a solvatochromism effect for all three rotors and their absorption and emission spectra were analyzed via the Lippert-Mataga equation and multilinear analysis using Kamlet-Taft and Catalán parameters. The rotors exhibited red-shifted absorption and emission bands in solution on account of differences in their torsion angle. The three rotors demonstrated strong fluorescence in a high-viscosity environment due to restricted intramolecular rotation. Investigations carried out under varying ratios of water to glycerol were explored to probe the viscosity-based changes in their optical properties. A good linear correlation between the logarithms of fluorescence intensity and solution viscosity for two rotors, namely 2DiAC∙Cl and 9DiAC∙Cl, was observed as the percentage of glycerol increased. Excellent exponential regression between the viscosity-related temperature and emission intensity was observed for all three investigated rotors.

A dual-emission fluorescence probe for the detection of viscosity and hydrazine in environmental and biological samples

The microenvironments of biological systems are associated with the pathology of organisms. This study, aimed to construct a hemicyanine-based probe (1), which can respond to mitochondrial viscosity and hydrazine (N2H4), for imaging application in living cells and zebrafish. The probe showed no fluorescence due to the intramolecular rotation in the solution; however, it exhibited a strong emission at 730 nm when the molecules were restricted to a high-viscosity environment. The addition of N2H4 caused an elimination reaction of the N-substituted group in the pyridinium part and further broke the CC bond to produce a highly fluorescent hydrazone. Also, the probe could selectively and quantitatively detect N2H4 via the fluorescence enhancement at 510 nm in a concentration range of 0 μM–140μM, with the limit of detection being 0.0485 μM. This probe may be used to study diseases related to N2H4 and viscosity changes in biological systems. Furthermore, the analysis methods based on probe 1 for N2H4 detection in soil, water, and air samples were successfully established.

A fluorescent probe for imaging nitroreductase with signal amplification in high-viscosity environments.

Herein, we developed a fluorescent probe ENBT for in vitro detection of nitroreductase (NTR) as well as imaging intracellular NTR. ENBT itself is non-fluorescent and it could be catalyzed by NTR to generate a viscosity-sensitive fluorophore EBT. The fluorescence intensity of EBT could be further enhanced in cancer cells with relatively high viscosity due to the inhibition of the twisted intramolecular charge transfer effect. The probe ENBT has a good response to NTR with a detection limit of 36.8 ng mL-1, and EBT has a good response to viscosity. Furthermore, different concentrations of NTR (0-1.4 μg mL-1) were used to react with the probe and the reaction systems were subjected to different viscosity solutions, and the fluorescence signals of the products in the viscosity range of 45.86-163.60 cP were increased up to 1.69-fold. ENBT was successfully used to image NTR in cells under different hypoxic conditions as well as in Staphylococcus aureus. Finally, lipopolysaccharide was added to stimulate an increase in cellular viscosity after ENBT was catalyzed by intracellular NTR into EBT, and the fluorescence signals were observed to increase by 1.72-fold. The signal amplification capability gives ENBT higher sensitivity and immunity to interference. Moreover, it has the advantages of mitochondrial targeting, large Stokes shift (190 nm), high selectivity, and can be easily synthesized.

Extracellular Hydraulic Resistance Enhances Cell Migration.

Cells migrating in vivo encounter microenvironments with varying physical properties. One such physical variable is the fluid viscosity surrounding the cell. Increased viscosity is expected to increase the hydraulic resistance experienced by the cell and decrease cell speed. The authors demonstrate that contrary to this expected result, cells migrate faster in high viscosity media on 2‐dimensional substrates. Both actin dynamics and water dynamics driven by ion channel activity are examined. Results show that cells increase in area in high viscosity and actomyosin dynamics remain similar. Inhibiting ion channel fluxes in high viscosity media results in a large reduction in cell speed, suggesting that water flux contributes to the observed speed increase. Moreover, inhibiting actin‐dependent vesicular trafficking that transports ion channels to the cell boundary changes ion channel spatial positioning and reduces cell speed in high viscosity media. Cells also display altered Ca2+ activity in high viscosity media, and when cytoplasmic Ca2+ is sequestered, cell speed reduction and altered ion channel positioning are observed. Taken together, it is found that the cytoplasmic actin‐phase and water‐phase are coupled to drive cell migration in high viscosity media, in agreement with physical modeling that also predicts the observed cell speedup in high viscosity environments.