Dynamically Monitoring Cell Viability in a Dual-Color Mode: Construction of an Aggregation/Monomer-Based Probe Capable of Reversible Mitochondria-Nucleus Migration

Article abstract of DOI:10.1002/anie.201811459

Mitochondria and nucleus play crucial roles during cell apoptosis process. In this work, a unique fluorescent probe capable of reversible migration between mitochondria and nucleus, as well as detection of cell viability in a dual-color mode is presented. The dual-color probe targets mitochondria in healthy cells, to form aggregates with deep-red emission. It migrates into nucleus and binds to DNA to form monomers with green fluorescence during apoptosis. Interestingly, the migration is reversible dependent on cell viability, which enables the dynamic visualization of apoptosis process. With the probe, mitochondria and nucleus can be visualized in dual colors during apoptosis, and the cell viability could be monitored by the emission color and localization of the probe.

Full text of DOI:10.1002/anie.201811459

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Accepted Article
Title: Dynamically Monitoring Cell Viability in a Dual-Color Mode:
Construction of an Aggregation/Monomer-Based Probe Capable
of Reversible Mitochondria-Nucleus Migration
Authors: Minggang Tian, Jie Sun, Baoli Dong, and Weiying Lin
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201811459
Angew. Chem. 10.1002/ange.201811459
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10.1002/anie.201811459
Angewandte Chemie International Edition
COMMUNICATION
Dynamically Monitoring Cell Viability in a Dual-Color Mode:
Construction of an Aggregation/Monomer-Based Probe Capable of
Reversible Mitochondria-Nucleus Migration
Minggang Tian, Jie Sun, Baoli Dong, and Weiying Lin*
Abstract: Mitochondria and nucleus play crucial roles during cell
apoptosis process. In this work, a unique fluorescent probe capable
of reversible migration between mitochondria and nucleus, as well as
detection of cell viability in a dual-color mode is presented. The dual-
color probe targets mitochondria in healthy cells, to form aggregates
with deep-red emission. It migrates into nucleus and binds to DNA to
form monomers with green fluorescence during apoptosis.
Interestingly, the migration is reversible dependent on cell viability,
which enables the dynamic visualization of apoptosis process. With
the probe, mitochondria and nucleus can be visualized in dual colors
during apoptosis, and the cell viability could be monitored by the
emission color and localization of the probe.
to the unique advantages including capability of in situ and real-
time visualization in live cells, low damage to biosamples, and
permission of dynamically analyzing live samples.[16,17] For
example, Kim et al. have designed and synthesized
a
mitochondria immobilized fluorescent probe to investigate the
mitochondrial dynamics during mitophagy processes.[18] Teulade-
Fichou and co-workers have developed two-photon fluorescent
probes for the imaging of cell nucleus.[19] Eliseeva et al. have
presented a near infrared fluorescent probe for the discrimination
of dead cells.[20]
Monitoring cell viability is a highly valuable task essential for the
fundamental researches in biology, pathology, and medicine.[1,2]
For instance, detecting the cell viability is necessary to evaluate
the efficacy of drugs and the cytotoxicity of biological reagents,
including antibiotics, drugs, nanoparticles, and fluorophores.[3-6]
Meanwhile, changing of cell viability such as apoptosis and
necrosis process under physiological conditions is indispensable
to maintain the homeostasis of cell population, and to defend
organisms in immune reactions.[7] Mitochondria and nucleus play
significant roles in the change of cellular status, especially in
apoptosis process.[8] According to the recent reports, the
signalling process of apoptosis initiates from the changes in cell
nucleus, including DNA damages and oncogene activation.[8]
Meanwhile, the execution of cell apoptosis starts from
mitochondria.[9,10] Mitochondria contain harmful proteins, reactive
oxygen species, and some other toxic compounds, which are
maintained inside mitochondria by their double membranes in
healthy cells. During cell apoptosis, sudden change in the
membrane permeability would occur and these toxic compounds
could be released to the cytoplasm and trigger the apoptosis
process.
To in-depth explore the relationship among mitochondria,
nucleus, and cell viability, visualization of the two organelles and
simultaneous detection of cell viability are greatly helpful. Up to
now, scanning electron microscope, transmission electron
microscope, colorimetric analysis, optical microscope, and many
other tools have been widely used to study mitochondria, nucleus,
and cell viability.[11-15] Compared with these techniques,
fluorescence imaging methods assisted with proper fluorescent
probes have received considerable interest in recent years, owing
Scheme 1. (a) The sensing mode of the mitochondria-nucleus migration probe
for detecting cell viability. (b) The design strategy of MNQI.
Recently, Kawamata’s group, Yu’s group, and Tian’s group
have developed fluorescent probes which target mitochondria in
healthy cells and gradually migrate into nucleus/nucleolus during
apoptosis.[21-23] The fluorescence wavelengths of those probes
remain unchanged in mitochondria and nucleus. However, these
intensity-based probes have some limitations, such as the
interferences from inhomogeneous staining of probes and
fluctuation of excitation intensity.[16] To avoid these limitations, it
is essential to discriminatively visualize mitochondria and nucleus
in dual emission colors. Unfortunately, fluorescent probes
capable of visualization of mitochondria and nucleus in dual
emission channels, and simultaneously enabling the detection of
cell viability have not been reported yet, which is an extremely
challenging task.
In this work, we have designed and synthesized a fluorescent
probe MNQI based on aggregation/monomer mechanism, for the
visualization of the two organelles in dual channels, and the
detection of cell viability. In Scheme 1, MNQI was constructed
with a weak electronic donor and a cationic quinolinium group. It
was a hydrophobic cation in nature which could be enriched in
mitochondria with high negative MMP in healthy cells. Moreover,
due to its structural similarity to PIC[24] and high concentration in
Dr. M. Tian, J. Sun, Dr. B. Dong, Prof. W. Lin
Institute of Fluorescent Probes for Biological Imaging, School of Chemistry
and Chemical Engineering, School of Materials Science and Engineering,
University of Jinan, Jinan, Shandong 250022, People’s Republic of China
E-mail: weiyinglin2013@163.com
Supporting information for this article is given via a link at the end of the
document.
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10.1002/anie.201811459
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mitochondria, MNQI forms aggregates with deep-red (DR)
emission in healthy cells.
bound to the minor grooves of DNA, and the binding energy was
calculated as -12.0 kcal/mol. These results indicate the desirable
affinity to DNA of MNQI, which is comparable to Hoechst 33342.
The planar structure and electronic structure of MNQI should be
responsible for its high affinity to DNA.
The electronic structure of MNQI resembles Hoechst, with a
weak electronic donor and a positively charged group. This
similarity endows MNQI high affinity to DNA. Therefore, with the
decrease of MMP in unhealthy status, the probe could be
released from mitochondrial and migrate into nucleus to form
monomers in DNA with green fluorescence. The migration of
MNQI between mitochondria and nucleus is dependent on MMP
and reversible. Consequently, cell viability could be evaluated by
the localization and intracellular emission color of MNQI.
The optical properties of the probe were initially investigated.
According to the molecular design, a prerequisite is that the probe
displays different emission wavelengths in the aggregation and
monomer states. Consequently, the absorption and fluorescence
spectra of MNQI in different organic solvents were acquired to
check the optical properties of its monomers. Simultaneously, the
emission spectra in buffer solutions and the solid state were also
obtained to explore the property of its aggregates. As shown in
Figure 1a and S1, MNQI displays strong absorbance in 350-500
nm and emission peaked around 570 nm in organic solvents. The
probe shows blue-shifted absorption and weak emission peaked
at 570 nm in buffer solutions, indicating that it forms H-aggregates
in aqueous conditions. Fortunately, MNQI exhibits strong
fluorescence peaked at 690 nm in solid state. Thus, MNQI shows
emission peaked at 570 nm and 690 nm in organic solvents and
solid states, respectively, demonstrating that the probe could give
dual emission colors in aggregation and monomer states.
To testify the mechanism of the red shift in aggregation state of
MNQI, its crystal has been prepared and analysed to investigate
the packing mode in solid state. In Figure 1b and 1c, the
molecules of MNQI are anti-parallelly stacked and form dimers in
the crystalline state, due to intermolecular electrostatic
interactions. The short intermolecular stacking distances of the
dimer are 3.364 Å, 3.340 Å, and 3.312 Å, indicating strong
intermolecular interactions inside the dimer. Moreover, the short
stacking distances between dimers are 3.374 Å and 3.390 Å,
demonstrating that interactions also exist between the dimers.
Consequently, the red shift in solid state should be attributed to
the intermolecular π-π interactions induced by the short contact
between the molecules.
In order to target cell nucleus, the probe should exhibit high
affinity to DNA, since the majority of cellular DNA exists in the
nucleus. Therefore, the DNA titration experiments have been
performed with MNQI. In Figure S2, MNQI displays rather weak
fluorescence in buffer solution, owing to the formation of H-
aggregates. With the addition of DNA, the fluorescence gradually
enhanced to 6-fold, because of the formation of monomers when
binding to DNA. The binding coefficient (k) is calculated as 4.1 ×
106 M-1, following the Scatchard equation (Figure S2), indicating
its high affinity to DNA that is slightly lower than Hoechst 33342
(2 × 107 M-1),[25] a commercial probe for DNA.
To explore the binding mechanism of MNQI to DNA in
molecular level, molecular docking calculations based on the
crystal structure of MNQI and DNA have been performed using
AutoDock 4.2 software[26]. In Figure 1a, MNQI bound to the minor
grooves of DNA, and the binding energy was calculated to be -
9.45 kcal/mol. The binding of Hoechst 33342 to DNA has been
also calculated for comparison. In Figure S3, Hoechst 33342 also
Figure 1. (a) The absorption and fluorescence spectra of 10 μM MNQI in ethanol,
DNA solutions, and solid states, and the binding mode to DNA. λex = 488 nm.
The top view (b) and side view (c) of the crystal structure of MNQI.
In consideration of the strong affinity to DNA and positively
charged nature of MNQI, the probe ought to target nucleus and
mitochondria in cells. Before cell imaging applications, the
cytotoxicity of MNQI to live cells has been initially testified using
MTT assay. In Figure S4, treatment with 1-15 μM MNQI for 24 h
brings little toxicity to live cells, and cell viability is above 90 %.
Thus, the cytotoxicity of 4 μM MNQI could be ignored with the
incubation time in 1 h.
Live cells were stained with the probe and imaged in dual
channels to check the localization of the probe. In Figure S5a,
MNQI distributed in cytoplasm of live cells and gave strong
fluorescent signals in the DR channel, while displayed weak
emission in the green channel. Meanwhile, the DR fluorescence
appeared as filament morphologies in cytoplasm, indicating the
staining of mitochondria in live cells. The in situ fluorescence
spectra have also been obtained using the spectral imaging
function of the confocal microscope. In Figure S6, intracellular
emission was peaked around 670 nm, resembling that of solid
MNQI, and proving the formation of aggregates like the solid state.
Furthermore, fixed HeLa cells have also been stained with
MNQI and imaged. In Figure S5a, MNQI stained the nucleus in
fixed cells and displayed strong fluorescence only in the green
channel. The in situ fluorescence spectra of MNQI in dead cells
have also been acquired, and in Figure S6 the emission was
peaked around 580 nm, similar with that in organic solvents and
DNA solutions. These results proved that MNQI stained nucleus
in fixed cells and presented in monomer state.
To accurately confirm the localization of MNQI in live and fixed
cells, co-localization experiments with MTDR and Hoechst 33342,
the commercialized probes for mitochondria and nucleus, have
been performed. In Figure 2, the fluorescent signals from MNQI
in live cells overlap well with that of MTDR, and the co-localization
coefficient is up to 0.90, indicating that MNQI actually stained
mitochondria in live cells. Moreover, the green emission from
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10.1002/anie.201811459
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MNQI in dead cells shows large overlap to the blue signals from
Hoechst 33342, with the co-localization coefficient of 0.91,
demonstrating that MNQI selectively stained nucleus in fixed cells.
Therefore, MNQI can discriminate live and fixed cells through the
localization and emission color of intracellular fluorescent signals.
Figure 2. The images of live and fixed HeLa cells co-stained with 4 μM MNQI
and commercial probes (200 nM MTDR for live cells, 2 μM Hoechst 33342 for
fixed cells) for 60 min. MNQI in live cells: λex = 488 nm, λem = 570-620 nm; MTDR:
λex = 647 nm, λem = 663-738 nm; MNQI in dead cells: λex = 488 nm, λem = 500-
550 nm; Hoechst 33342: λex = 405 nm, λem = 425-475 nm. Bar = 10 μm.
Figure 3. Fluorescence images of HeLa cells pre-stained with 4 μM MNQI for
60 min, (a) treated with 20 μM CCCP for 0-7 min, and then (b) CCCP was
washed away and incubated with culture medium for another 1-12 min. (c) The
time-dependent intensity ratio of green channel to DR channel in (a) and (b). λex
= 488 nm; green channel: λem = 500-550 nm; DR channel: λem = 663-738 nm.
Bar = 10 μm.
MNQI targets mitochondria and nucleus in live and fixed cells,
respectively. We speculate that the distribution of MNQI is
determined by the MMP levels. In live cells with high MMP, MNQI
mainly exists in mitochondria due to the electrophoresis effect. In
dead cells with almost no MMP, MNQI targets nucleus due to the
affinity to DNA. To prove the speculation, healthy HeLa cells were
prestained with MNQI, and then treated with CCCP, a regent that
can decrease MMP rapidly. In Figure 3a and Movie S1, MNQI
initially stained mitochondria with DR emission in healthy cells.
With the addition of CCCP and decrease of MMP levels, MNQI
was released from mitochondria and migrated to the nucleus with
green emission. Subsequently, MMP levels could actually
influence the targets of MNQI. CCCP was afterwards removed
and MMP levels could be recovered. In Figure 3b, after the
removal of CCCP, the green emission in nucleus gradually
disappeared, indicating that MNQI migrated back into
mitochondria. This procedure can be semi-quantified by the ratio
of green to DR signals shown in Figure 3c. These results indicate
that MNQI could reversibly detect the changes of MMP levels from
both the localization and the emission color. Considering that
MMP levels could directly reflect the cell viability, MNQI is
potential to report the cell viability reversibly.
Excessive amount of hydrogen peroxide could inhibit the
oxidation respiratory chain and induce cell damage.[27] To verify
the ability of MNQI in visualization of cell viability, healthy cells
pre-incubated with MNQI were treated with hydrogen peroxide
(Figure S7 and Movie S2). In Figure S7a, healthy cells displayed
strong DR emission in mitochondria and almost no emission in
nucleus. After the addition of hydrogen peroxide, cell viability was
decreased, and green emission in the nucleus steadily enhanced,
indicating the migration of MNQI from mitochondria to nucleus.
This process could be also monitored by the signal ratio of green
channels to DR ones, as plotted in Figure S7c. These results
confirmed that MNQI could serve a valid tool for visualizing the
decline of cell viability through both the localization and emission
color.
L-Ascorbic acid (VC) is a significant antioxidant resistant to
damage by ROS. Consequently, we conceived that VC may
recover the status of cells pretreated with hydrogen peroxide for
a short period of time. In Figure S7b, after the treatment for 15
min, hydrogen peroxide was removed and VC was added.
Obviously, the green emission in nucleus faded off, indicating the
migration of MNQI back into the mitochondria and the recovery of
cell viability. The process could also be monitored (Figure S7c) by
means of the intensity ratio between the two emission channels.
Therefore, MNQI can detect the reversible change of cell viability.
Rotenone is a toxicant that has been used as a broad-spectrum
pesticide, which can efficiently induce cell apoptosis.[28] Recent
studies revealed that rotenone worked by interfering with the
electron transport chain in mitochondria, and caused the excess
production of ROS.[28] To discover the potential application of
MNQI to discriminate apoptosis cells, live HeLa cells was
pretreated with rotenone for 24 h and then stained with the probe
(Figure 4a). Live cells in the control group untreated with rotenone
displayed intense DR emission in mitochondria and no
fluorescence in the nucleus. In comparison, cells treated with
rotenone displayed strong emission in green channel and
weakened fluorescence in DR channel, indicating cell apoptosis
and decreased viability. In Figure 7b, the ratio of green to DR
channel exhibited dramatic increase upon the treatment of
rotenone, also demonstrating the cell apoptosis.
Since rotenone induces cell apoptosis by promoting the
generation of elevated levels of ROS, VC may be able to relieve
the toxicity owing to its anti-oxidative characteristics.
Consequently, VC was added to cells pretreated with rotenone for
6 h, and then the cells were further cultured for another 18 h. In
Figure 5a, VC-treated cells display obviously weakened green
emission and enhanced DR fluorescence, compared with those
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10.1002/anie.201811459
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solely incubated with rotenone. This could also be clearly Conflict of interest
observed via the signal ratio of green to red channel (Figure 5b).
The authors declare no conflict of interest
.
Accordingly, MNQI could detect the apoptosis process induced by
rotenone, via the change of localization and emission color. The
effect of VC to relieve rotenone toxicity could also be visualized.
Keywords: fluorescent probe • cell viability • mitochondria •
nucleus • dual-color
Reference
[1]
O. Kepp, L. Galluzzi, M. Lipinski, J. Yuan, G. Kroemer, Nat. Rev. Drug
Discov. 2011, 10, 221-237.
[2]
[3]
V. Vichai, K. Kirtikara, Nat. Protoc. 2006, 1, 1112-1116.
V. M. Steffes, M. M. Murali, Y. Park, B. J. Fletcher, K. K. Ewert, C. R.
Safinya, Biomaterials 2017, 145, 242-255.
[4]
R. Alford, H. M. Simpson, J. Duberman, G. C. Hill, M. Ogawa, C. Regino,
H. Kobayashi, P. L. Choyke, Mol. Imaging 2009, 8, 341-354.
N. Lewinski, V. Colvin, R. Drezek, Small 2008, 4, 26-49.
F. Valeriote, P. L. Van, Cancer Res. 1975, 35, 2619.
S. Elmore, Toxicol. Pathol. 2007, 35, 495-516.
[5]
[6]
[7]
[8]
E. A. Prokhorova, A. V. Zamaraev, G. S. Kopeina, B. Zhivotovsky, I. N.
Lavrik, Cell. Mol. Life Sci. 2015, 72, 4593-4612.
Figure 4. (a) DIC and fluorescent images of HeLa cells stained with 4 μM MNQI
for 60 min after the incubation with different regents, and (b) the corresponding
intensity ratio of green channel to DR channel. Control group: HeLa cells were
treated with DMSO for 24 h; “Rot” group: HeLa cells were incubated with 5 μM
rotenone for 24 h; “Rot+VC” group: HeLa cells were treated with 5 μM rotenone
for 6 h, then 100 μM VC was added, and the cells were incubated for another
18 h. λex = 488 nm; green channel: λem = 500-550 nm; DR channel: λem = 663-
738 nm. Bar = 10 μm.
[9]
S. W. Tait, D. R. Green, Nat. Rev. Mol. Cell Biol. 2010, 11, 621-632.
[10] N. Zamzami, G. Kroemer, Nat. Rev. Mol. Cell Biol. 2001, 2, 67-71.
[11] G. Repetto, A. del Peso, J. L. Zurita, Nat. Protoc. 2008, 3, 1125-1131.
[12] M. L. Joiner, O. M. Koval, J. Li, B. J. He, C. Allamargot, Z. Gao, E. D.
Luczak, D. D. Hall, B. D. Fink, B. Chen, J. Yang, S. A. Moore, T. D.
Scholz, S. Strack, P. J. Mohler, W. I. Sivitz, L. S. Song, M. E. Anderson,
Nature 2012, 491, 269-273.
[13] T. D. Allen, S. A. Rutherford, S. Murray, F. Gardiner, E. Kiseleva, M. W.
Goldberg, S. P. Drummond, Nat. Protoc. 2007, 2, 1180-1184.
[14] B. Glancy, L. M. Hartnell, D. Malide, Z. X. Yu, C. A. Combs, P. S.
Connelly, S. Subramaniam, R. S. Balaban, Nature 2015, 523, 617-620.
[15] H. Tominaga, M. Ishiyama, F. Ohseto, K. Sasamoto, T. Hamamoto, K.
Suzuki, M. Watanabe, Anal. Commun. 1999, 36, 47-50.
In conclusion, we have designed and synthesized an
aggregation/monomer-based fluorescent probe, MNQI, capable
of reversible migration between nucleus and mitochondria, and
visualization of dynamic changes in cell viability in a dual-color
mode. The cationic probe could stain mitochondria in healthy cells,
and form aggregates with DR-emissive properties. Along with the
decrease of cell viability, the novel probe could be released from
mitochondria and migrate into nucleus to emit green fluorescence
in monomer status. Meanwhile, with the recovery of the cell
viability, MNQI can reversibly move back to the mitochondria with
DR emission. Using this unique probe, the cell viability could be
dynamically and accurately visualized through the intracellular
localization and emission color. Particularly, the reversible
changes of cell viability have been successfully observed with the
probe. The cell apoptosis caused by toxic rotenone has been
detected using MNQI, and the inhibition effect of VC to rotenone
caused apoptosis was verified. We believe that MNQI can serve
as a powerful tool to investigate the internal relationship among
apoptosis, nucleus, and mitochondria, and promote the
fundamental researches in biology, pathology, and medicine.
[16] L. Yuan, W. Lin, K. Zheng, S. Zhu, Acc. Chem. Res. 2012, 46, 1462-
1473.
[17] R. Wayne, Chapter 11 - Fluorescence Microscopy, Elsevier Inc., 2014.
[18] M. H. Lee, N. Park, C. Yi, J. H. Han, J. H. Hong, K. P. Kim, D. H. Kang,
J. L. Sessler, C. Kang, J. S. Kim, J. Am. Chem. Soc. 2014, 136, 14136-
14142.
[19] B. Dumat, G. Bordeau, E. Faurel-Paul, F. Mahuteau-Betzer, N. Saettel,
G. Metge, C. Fiorini-Debuisschert, F. Charra, M. P. Teulade-Fichou, J.
Am. Chem. Soc. 2013, 135, 12697-12706.
[20] I. Martinic, S. V. Eliseeva, T. N. Nguyen, V. L. Pecoraro, S. Petoud, J.
Am. Chem. Soc. 2017, 139, 8388-8391.
[21] H. Moritomo, K. Yamada, Y. Kojima, Y. Suzuki, S. Tani, H. Kinoshita, A.
Sasaki, S. Mikuni, M. Kinjo, J. Kawamata, Cell Struct. Funct. 2014, 39,
125-133.
[22] X. Li, M. Tian, G. Zhang, R. Zhang, R. Feng, L. Guo, X. Yu, N. Zhao, X.
He, Anal. Chem. 2017, 89, 3335-3344.
[23] D. Liu, M. Zhang, W. Du, L. Hu, F. Li, X. Tian, A. Wang, Q. Zhang, Z.
Zhang, J. Wu, Y. Tian, Inorg. Chem. 2018, 57, 7676-7683.
[24] N. J. Hestand, F. C. Spano, Chem. Rev. 2018, 118, 7069-7163.
[25] R. S. Harapanhalli, L. W. McLaughlin, R. W. Howell, D. V. Rao, S. J.
Adelstein, A. I. Kassis, J. Med. Chem. 1996, 39, 4804-4809.
[26] G. M. Morris, R. Huey, W. Lindstrom, M. F. Sanner, R. K. Belew, D. S.
Goodsell, A. J. Olson, J. Comput. Chem. 2009, 30, 2785-2791.
[27] M. Das, S. B. Mukherjee, C. Shaha, J. Cell Sci. 2001, 114, 2461-2469.
[28] N. Li, K. Ragheb, G. Lawler, J. Sturgis, B. Rajwa, J. A. Melendez, J. P.
Robinson, J. Biol. Chem. 2003, 278, 8516-8525.
Acknowledgements
This work was financially supported by NSFC (21472067,
21672083, 21877048, 21804052), Taishan Scholar Foundation
(TS201511041), NSF of Shandong Province (ZR2018BB058),
and the startup fund of University of Jinan (309-10004,
160100331).
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Entry for the Table of Contents (Please choose one layout)
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Visualizing cell viability in dual-
Minggang Tian, Jie Sun, Baoli Dong,
and Weiying Lin*
color mode:
A fluorescent probe
capable of reversible migration
between mitochondria and nucleus
dependent on cell viability and labelling
the two organelles in dual colors has
been developed. With the probe,
mitochondria and nucleus can be
visualized in dual emission channels,
and cell viability could be evaluated by
intracellular emission color and probe
localization.
Page No. – Page No.
Dynamically Monitoring Cell Viability
in a Dual-Color Mode: Construction of
an Aggregation/Monomer-Based
Fluorescent Probe Capable of
Reversible Mitochondria-Nucleus
Migration
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