A novel fluorescent protein chromophore analogue to simultaneously probe lysosome viscosity and β-amyloid fibrils

Sun, Han; Leng, Huaxiang; Liu, Jinsheng; Roy, Gaurab; Yan, Jin-wu; Zhang, Lei

doi:10.1016/j.snb.2019.127509

Cited by 36 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Structural Optimization of FP Chromophore Analogue for Noncovalent Detection. Bioinspired FP chromophore analogues (Figure 2a, A1) have attracted extensive attention recently as they are fluorogenic when embedded in DNA, 33 lysosome, 34 and protein-binding pocket 35 by inhibiting the twisted intramolecular charge transfer. The core structure of these mimics (A1) is of exclusive fluorescence in the crystalline solid (Figure S1).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores

et al. 2020

View full text Add to dashboard Cite

Stress-induced intracellular proteome aggregation is a hallmark and a biomarker of various human diseases. Current sensors requiring either cellular fixation or covalent modification of the entire proteome are not suitable for live-cell applications and dynamics study. Herein, we report a noncovalent, cell-permeable, and fluorogenic sensor that can reversibly bind to proteome amorphous aggregates and monitor their formation, transition, and clearance in live cells. This sensor was structurally optimized from previously reported fluorescent protein chromophores to enable noncovalent and reversible binding to aggregated proteins. Unlike all previous sensors, the noncovalent and reversible nature of this probe allows for dynamic detection of both the formation and clearance of aggregated proteome in one live-cell sample. Under different cellular stresses, this sensor reveals drastic differences in the morphology and location of aggregated proteome. Furthermore, we have shown that this sensor can detect the transition from proteome liquid-to-liquid phase separation to liquid-to-solid phase separation in a two-color imaging experiment. Overall, the sensor reported here can serve as a facile tool to screen therapeutic drugs and identify cellular pathways that ameliorate pathogenic proteome aggregation in live-cell models.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Therefore, it is still urgent and of great significance to develop new strategies to realize the early detection and diagnosis of AD. Besides, intracellular viscosity is an important indicator for evaluating the cell state, , and slight changes in intracellular viscosity, including lipid droplets and lysosomal viscosity, − are also related to Alzheimer’s disease. It is obvious that the dual-function probes for AD diagnosis and treatment might have a wider application prospect, for example, probes for Aβ and viscosity in our previous review .…”

Section: Introductionmentioning

confidence: 99%

Rotor-Tuning Boron Dipyrromethenes for Dual-Functional Imaging of Aβ Oligomers and Viscosity

Wang

Yang

Chen

et al. 2022

ACS Appl. Bio Mater.

Self Cite

View full text Add to dashboard Cite

Alzheimer's disease (AD), known as a common incurable and elderly neurodegenerative disease, has been widely explored for accurate detection of its biomarker (Aβ oligomers) for early diagnosis. Although great efforts have been made, it is still of great importance to develop fluorescence probes for Aβ oligomers with good selectivity and low background. Herein, starting from BODIPY493/503 (a commercial dye for neutral lipid droplets), which exhibited a small Stokes shift and no response toward Aβ peptides, two fluorescence probes 5MB-SZ and B-SZ with a benzothiazole rotor at the 2-position of the BODIPY core and a methyl or benzyl group at the meso position have been designed and synthesized, which exhibited excellent optical properties/stability and could successfully image β-amyloid fibrils and viscosity. Upon exposure to Aβ oligomers, the fluorescence intensity of 5MB-SZ was enhanced by 43.64-fold with the corresponding fluorescence quantum yields changing from 0.85% to 27.43%. Meanwhile, probe 5MB-SZ showed a highly sensitive viscosity response in both solutions and living cells. In vitro and in vivo experiments confirmed that probe 5MB-SZ exhibited an excellent capacity for imaging β-amyloid fibrils. Therefore, 5MB-SZ, as a rotor-tuning BODIPY analogue, could possibly serve as a highly potential and powerful fluorescence probe for early diagnosis of AD.

show abstract

“…Owing to the real-time imaging, high sensitivity, high selectivity, and noninvasive detection, activity-based small molecular fluorescent probes have emerged as effective tools for monitoring the bioanalytes not only in subcellular organelles but also in vivo. − To date, there have been many excellent fluorescent probes for detecting HOCl in the lysosomes, which are primarily due to the basic groups for guiding the probes to lysosomes and the oxidation property of probes for detecting HOCl. − In addition, a great deal of well-designed fluorescent probes for visualizing the changes of viscosity in lysosomes have been reported, which are based mainly on the twisted internal charge transfer (TICT) effect. − In contrast to the simple combination of two kinds of fluorescent probes in one system, dual-responsive fluorescent probes for detecting multiple analytes with different wavelengths in a single molecule can overcome several limitations, including diverse localizations, various metabolisms, and fluorescence cross-talk …”

mentioning

confidence: 99%

Simultaneous Monitoring of HOCl and Viscosity with Drug-Induced Pyroptosis in Live Cells and Acute Lung Injury

et al. 2022

View full text Add to dashboard Cite

Pyroptosis is a newly identified form of cell death that is closely correlated with many diseases. Recent studies have indicated that the inflammation in pyroptosis would accelerate the generation of reactive oxygen species (ROS). In addition, intracellular viscosity is another key microenvironmental parameter that reflects many physiological and pathological states in the early stage, hypochlorous acid (HOCl), as an important ROS, also plays significant roles in a variety of pathologies. However, the fluctuation of viscosity and HOCl in the process of pyroptosis is still unknown. Herein, we present a dual-responsive fluorescent probe (Lyso-VH) for simultaneously detecting viscosity and HOCl. Lyso-VH was successfully used to image the fluctuation of HOCl and viscosity in the lysosome of three kinds of cells with dependent and independent channels. Moreover, Lyso-VH can be employed to investigate the changes of HOCl and viscosity during the process of pyroptosis in living cells and acute lung injury (ALI). Thus, this work can not only serve as a powerful tool to simultaneously visualize the fluctuation of HOCl and viscosity in lysosomes, but also provide a new insight into drug-induced pyroptosis in living cells and acute lung injury.

show abstract

A novel fluorescent protein chromophore analogue to simultaneously probe lysosome viscosity and β-amyloid fibrils

Cited by 36 publications

References 25 publications

Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores

Monitoring the Dynamics of Proteome Aggregation in Live Cells Using a Solubilized and Noncovalent Analogue of Fluorescent Protein Chromophores

Rotor-Tuning Boron Dipyrromethenes for Dual-Functional Imaging of Aβ Oligomers and Viscosity

Simultaneous Monitoring of HOCl and Viscosity with Drug-Induced Pyroptosis in Live Cells and Acute Lung Injury

Contact Info

Product

Resources

About