A highly selective AIE fluorogen for lipid droplet imaging in live cells and green algae.

Lipid droplets (LDs) are subcellular organelles for energy storage and lipid metabolism regulation. Here we report an aggregation-induced emission-active fluorogen, TPE-AmAl, for specific LD imaging. TPE-AmAl is cell-permeable: upon entering the live cells, the dye molecules can selectively accumulate in the LDs and turn on the fluorescence. TPE-AmAl possesses twisted intramolecular charge transfer properties as well: the emission colour in the hydrophobic LDs is blue-shifted by >100 nm than that in aqueous buffers. Compared with the commercial lipid droplet dye, TPE-AmAl demonstrates the advantages of low background, short staining time, high selectivity, excellent biocompatibility, and good photostability. The utilization of TPE-AmAl for LD staining in green algae is also demonstrated, indicating their potential application in the high-throughput screening of high-value microalgae as a preferential biofuel source.

[1]  Kam Sing Wong,et al.  A tetraphenylethene-substituted pyridinium salt with multiple functionalities: synthesis, stimuli-responsive emission, optical waveguide and specific mitochondrion imaging , 2013 .

[2]  J. McManaman,et al.  Dynamic Regulation of Hepatic Lipid Droplet Properties by Diet , 2013, PloS one.

[3]  Sanghee Lee,et al.  Discovery of autophagy modulators through the construction of a high-content screening platform via monitoring of lipid droplets , 2013 .

[4]  Ryan T. K. Kwok,et al.  Long-term fluorescent cellular tracing by the aggregates of AIE bioconjugates. , 2013, Journal of the American Chemical Society.

[5]  V. Barone,et al.  Unraveling the peculiar modus operandi of a new class of solvatochromic fluorescent molecular rotors by spectroscopic and quantum mechanical methods , 2013 .

[6]  Sangcheol Na,et al.  Optimization of Seoul-Fluor-based lipid droplet bioprobes and their application in microalgae for bio-fuel study. , 2013, Molecular bioSystems.

[7]  B. Tang,et al.  Full-range intracellular pH sensing by an aggregation-induced emission-active two-channel ratiometric fluorogen. , 2013, Journal of the American Chemical Society.

[8]  Ben Zhong Tang,et al.  A photostable AIE luminogen for specific mitochondrial imaging and tracking. , 2013, Journal of the American Chemical Society.

[9]  Pingsheng Liu,et al.  Isolating lipid droplets from multiple species , 2012, Nature Protocols.

[10]  B. Tang,et al.  Tetraphenylethene: a versatile AIE building block for the construction of efficient luminescent materials for organic light-emitting diodes , 2012 .

[11]  D. Ding,et al.  Aggregation-induced red-NIR emission organic nanoparticles as effective and photostable fluorescent probes for bioimaging , 2012 .

[12]  Kam Sing Wong,et al.  An AIE-active hemicyanine fluorogen with stimuli-responsive red/blue emission: extending the pH sensing range by “switch + knob” effect , 2012 .

[13]  Sanghee Lee,et al.  A Seoul-Fluor-based bioprobe for lipid droplets and its application in image-based high throughput screening. , 2012, Chemical communications.

[14]  Daniel‐Adriano Silva,et al.  Monitoring and inhibition of insulin fibrillation by a small organic fluorogen with aggregation-induced emission characteristics. , 2012, Journal of the American Chemical Society.

[15]  B. Tang,et al.  Luminogenic materials constructed from tetraphenylethene building blocks: Synthesis, aggregation-induced emission, two-photon absorption, light refraction, and explosive detection , 2012 .

[16]  Ben Zhong Tang,et al.  Aggregation-induced emission. , 2011, Chemical Society reviews.

[17]  Pingsheng Liu,et al.  Proteome of skeletal muscle lipid droplet reveals association with mitochondria and apolipoprotein a-I. , 2011, Journal of proteome research.

[18]  J. Hamman,et al.  Natural products in anti-obesity therapy. , 2011, Natural product reports.

[19]  I. Nishino,et al.  Lipid Storage Myopathy , 2011, Current neurology and neuroscience reports.

[20]  H. Tissenbaum,et al.  A Comparative Study of Fat Storage Quantitation in Nematode Caenorhabditis elegans Using Label and Label-Free Methods , 2010, PloS one.

[21]  R. Wijffels,et al.  An Outlook on Microalgal Biofuels , 2010, Science.

[22]  Michitaka Suzuki,et al.  A pitfall in using BODIPY dyes to label lipid droplets for fluorescence microscopy , 2010, Histochemistry and Cell Biology.

[23]  G. Ruvkun,et al.  C. elegans major fats are stored in vesicles distinct from lysosome-related organelles. , 2009, Cell metabolism.

[24]  J. Peychl,et al.  Live Cell Multicolor Imaging of Lipid Droplets with a New Dye, LD540 , 2009, Traffic.

[25]  Ben Zhong Tang,et al.  Acetylenic polymers: syntheses, structures, and functions. , 2009, Chemical reviews.

[26]  B. Tang,et al.  Aggregation-induced emission: phenomenon, mechanism and applications. , 2009, Chemical Communications.

[27]  Gong Peng,et al.  A role for lipid droplets in inter‐membrane lipid traffic , 2009, Proteomics.

[28]  L. Woollett,et al.  A high throughput live transparent animal bioassay to identify non-toxic small molecules or genes that regulate vertebrate fat metabolism for obesity drug development , 2008, Nutrition & metabolism.

[29]  Kevin Burgess,et al.  BODIPY dyes and their derivatives: syntheses and spectroscopic properties. , 2007, Chemical reviews.

[30]  R. Bartenschlager,et al.  The lipid droplet is an important organelle for hepatitis C virus production , 2007, Nature Cell Biology.

[31]  S. Boulant,et al.  Disrupting the association of hepatitis C virus core protein with lipid droplets correlates with a loss in production of infectious virus. , 2007, The Journal of general virology.

[32]  Ian D. Williams,et al.  Aggregation-induced and crystallization-enhanced emissions of 1,2-diphenyl-3,4-bis(diphenylmethylene)-1-cyclobutene. , 2007, Chemical communications.

[33]  Yongqiang Dong,et al.  Fluorescence enhancements of benzene-cored luminophors by restricted intramolecular rotations: AIE and AIEE effects. , 2007, Chemical communications.

[34]  S. Yamaguchi,et al.  Long-chain fatty acids induce lipid droplet formation in a cultured human hepatocyte in a manner dependent of Acyl-CoA synthetase. , 2006, Biological & pharmaceutical bulletin.

[35]  Paul Zimmet,et al.  The metabolic syndrome—a new worldwide definition , 2005, The Lancet.

[36]  Ian D. Williams,et al.  Structural control of the photoluminescence of silole regioisomers and their utility as sensitive regiodiscriminating chemosensors and efficient electroluminescent materials. , 2005, The journal of physical chemistry. B.

[37]  P. Iyengar,et al.  Role of caveolin-1 in the modulation of lipolysis and lipid droplet formation. , 2004, Diabetes.

[38]  Wolfgang Rettig,et al.  Structural changes accompanying intramolecular electron transfer: focus on twisted intramolecular charge-transfer states and structures. , 2003, Chemical reviews.

[39]  Honey Chan,et al.  Peroxisome biogenesis occurs in an unsynchronized manner in close association with the endoplasmic reticulum in temperature-sensitive Yarrowia lipolytica Pex3p mutants. , 2003, Molecular biology of the cell.

[40]  R. Chapman To perform or not to perform liver biopsy—that is the question , 2002, Gut.

[41]  D. Murphy The biogenesis and functions of lipid bodies in animals, plants and microorganisms. , 2001, Progress in lipid research.

[42]  P. D. James,et al.  Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. , 2001, Journal of hepatology.

[43]  D. Brasaemle,et al.  TIP47 Associates with Lipid Droplets* , 2001, The Journal of Biological Chemistry.

[44]  S. Kohlwein,et al.  Identification and Characterization of Major Lipid Particle Proteins of the Yeast Saccharomyces cerevisiae , 1999, Journal of bacteriology.

[45]  T. Barber,et al.  Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes. , 1995, Journal of lipid research.

[46]  P. Gőcze,et al.  Factors underlying the variability of lipid droplet fluorescence in MA-10 Leydig tumor cells. , 1994, Cytometry.

[47]  G. Serrero,et al.  Isolation and characterization of a full-length cDNA coding for an adipose differentiation-related protein. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[48]  S. Fowler,et al.  Nile red: a selective fluorescent stain for intracellular lipid droplets , 1985, The Journal of cell biology.

[49]  W. Rettig Intramolecular rotational relaxation of compounds which form "twisted intramolecular charge transfer" (TICT) excited states , 1982 .

[50]  E. E. Lepherd,et al.  Size distribution of fat globules in cow's milk during milking, measured with a Coulter counter , 1969, Journal of Dairy Research.

[51]  Th. Förster,et al.  Ein Konzentrationsumschlag der Fluoreszenz des Pyrens , 1954, Zeitschrift für Elektrochemie, Berichte der Bunsengesellschaft für physikalische Chemie.

[52]  H. Inoko,et al.  Which CIDE are you on? Apoptosis and energy metabolism. , 2011, Molecular bioSystems.

[53]  Robert G. Parton,et al.  Opinion: Lipid droplets: a unified view of a dynamic organelle , 2006, Nature Reviews Molecular Cell Biology.

[54]  H S Kwok,et al.  Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. , 2001, Chemical communications.

[55]  A. Sesso,et al.  Sarcoplasmic lipase and non-specific esterase inhibition in myofibers of rats intoxicated with the organophosphate isofenphos. , 1999, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.