A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment

Owyong, Tze Cin; Subedi, Pramod; Deng, Jieru; Hinde, Elizabeth; Paxman, Jason J.; White, Jonathan M.; Chen, Weisan; Heras, Begoña; Wong, Wallace W. H.; Hong, Yuning

doi:10.1002/ange.201914263

Cited by 18 publications

(9 citation statements)

References 42 publications

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“…After the T-MY covalently bound to peptide, n- electronic conjugation of the maleimide group was destroyed. [43][44] Thus, RTP, (Supporting Information Figure S12). The successful synthesis and photophysical properties of these probes are significant to further explore the imaging ability of them on living cell membranes.…”

Section: Synthesis and Characterization Of Rtp Tp And Rtmentioning

confidence: 99%

Peptide-Conjugated Aggregation-Induced Emission Fluorogen: Precise and Firm Cell Membrane Labeling by Multiple Weak Interactions

Yang¹,

Hu²,

Wei³

et al. 2022

CCS Chem

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Cell membrane is a vital barrier to protect the cell from outside damage and involved in many biochemical processes. It is of great significance to label the cell membrane to explore its function. However, due to the complex and dynamic nature of cell membrane, precisely and firmly labeling the cell membrane simultaneously is still a challenge. Herein, we report a peptide-conjugated aggregation-induced emission fluorogen (AIEgen), named RTP. RTP mainly consists of three components. (1) RGD peptide (R), which can specifically bind to integrin  v  3 on cell membrane through ligand-receptor interaction. ( 2) T-MY (T), an AIE-active tetraphenylethene derivative for fluorescent imaging. (3) Palmitic acid modified peptide Pal-RRRR (P), in which Pal is inserted into the lipid on the cell membrane by hydrophobic interaction, and RRRR is combined with the negatively charged cell membrane through electrostatic interaction. RTP can precisely label the tumor cells with high integrin  v  3 expression, firmly trace the cell membrane for up to 4 hours, and has strong resistance to photobleaching. Moreover, RTP achieves tumor specific imaging by labeling cell membrane in vivo. Utilizing multiple weak interactions between the fluorescent probe and cell membrane provides a new strategy for precise and firm imaging of cell membrane simultaneously.

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Section: Synthesis and Characterization Of Rtp Tp And Rtmentioning

confidence: 99%

Peptide-Conjugated Aggregation-Induced Emission Fluorogen: Precise and Firm Cell Membrane Labeling by Multiple Weak Interactions

Yang¹,

Hu²,

Wei³

et al. 2022

CCS Chem

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“…However, these abovementioned stresses were hardly observed. To date, the development of environment-sensitive fluorophores tackles this issue by visualizing proteome aggregation in live cells.. Hong reported on series of covalent probes to detect unfolded proteome with the exposed thiols upon cellular stresses 45,46 . Zhang pioneered in uncovering the protein aggregation process via protein-based fluorogenic sensors 47,48 .…”

Section: Introductionmentioning

confidence: 99%

Plastic Nanoparticles Cause Proteome Stress and Aggregation by Compromising Cellular Protein Homeostasis ex vivo and in vivo.

Jing

Wan

et al. 2022

Preprint

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Decomposition of plastic materials into minuscule particles and their long-term uptake pose increasing concerns on environmental sustainability and biosafety. Besides common cell viability and cytotoxicity evaluations, how plastic nanoparticles interfere with different stress response pathways and affect cellular fitness has been less explored. Here, we provided the first piece of evidence to demonstrate plastic nanoparticles potentially can deteriorate proteome stability, compromise cellular protein homeostasis, and consequently cause global proteome misfolding and aggregation. Polystyrene (PS) nanoparticles of different sizes and surface charges were exploited as model plastic materials. In cell lysate and human blood plasma, naked PS nanoparticles with hydrophobic surface deteriorated proteome thermodynamic stability and exaggerated its aggregation propensity. While no cell viability ablation was observed in cells treated with PS nanoparticles up to 200 μg·mL-1, global proteome aggregation and stress was detected by a selective proteome aggregation sensor. Further proteomics analysis revealed how protein homeostasis network was remodeled by positively charged PS nanoparticles via differential expression of key proteins to counteract proteome stress. In mice model, size-dependent liver accumulation of positively charged PS nanoparticles induced hepatocellular proteome aggregation and compromised protein homeostasis network capacity that were invisible to standard ALT/AST liver function assay and histology. Meanwhile, long-term liver accumulation of plastic nanoparticles deteriorated liver metabolism and saturated liver detoxification capacity of overdosed acetaminophen. This work highlighted the impact of nanoplastics on cellular proteome integrity and cellular fitness that are invisible to current biochemical assays and clinical tests.

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“…Conjugation to peptides has been reported to endow sensing selectivity as well as improve the property of AIEgens. [ 22 ] In this study, as the majority of cytoplasmic unfolded proteins locate in the ER, [ 23 ] an ER targeting hydrophilic peptide was selected in the probe design. With the peptide, D1 possesses excellent water solubility and cell permeability, as well as highly bright emission and low background noise when reacting with unfolded proteins in live cells.…”

Section: Introductionmentioning

confidence: 99%

Construction of a Highly Sensitive Thiol‐Reactive AIEgen‐Peptide Conjugate for Monitoring Protein Unfolding and Aggregation in Cells

Sabouri

Liu

Zhang

et al. 2021

Adv Healthcare Materials

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Impairment of the protein quality control network leads to the accumulation of unfolded and aggregated proteins. Direct detection of unfolded protein accumulation in the cells may provide the possibility for early diagnosis of neurodegenerative diseases. Here a new platform based on a peptide‐conjugated thiol‐reactive aggregation‐induced emission fluorogen (AIEgen), named MI‐BTD‐P (or D1), for labeling and tracking unfolded proteins in cells is reported. In vitro experiments with model proteins show that the non‐fluorescent D1 only becomes highly fluorescent when reacted with the thiol group of free cysteine (Cys) residues on unfolded proteins but not glutathione or folded proteins with buried or surface exposed Cys. When the labeled unfolded proteins form aggregates, D1 fluorescence intensity is further increased, and fluorescence lifetime is prolonged. D1 is then used to measure unfolded protein loads in cells by flow cytometry and track the aggregate formation of the D1 labeled unfolded proteins using confocal microscopy. In combination with fluorescence lifetime imaging technique, the proteome at different folding statuses can be better differentiated, demonstrating the versatility of this new platform. The rational design of D1 demonstrates the outlook of incorporation of diverse functional groups to achieve maximal sensitivity and selectivity in biological samples.

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A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment

Cited by 18 publications

References 42 publications

Peptide-Conjugated Aggregation-Induced Emission Fluorogen: Precise and Firm Cell Membrane Labeling by Multiple Weak Interactions

Peptide-Conjugated Aggregation-Induced Emission Fluorogen: Precise and Firm Cell Membrane Labeling by Multiple Weak Interactions

Plastic Nanoparticles Cause Proteome Stress and Aggregation by Compromising Cellular Protein Homeostasis ex vivo and in vivo.

Construction of a Highly Sensitive Thiol‐Reactive AIEgen‐Peptide Conjugate for Monitoring Protein Unfolding and Aggregation in Cells

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