Quantum Dots Monitor TrkA Receptor Dynamics in the Interior of Neural PC12 Cells

Rajan, Sujata Sundara; Vu, Tania Q.

doi:10.1021/nl0612650

Cited by 62 publications

(49 citation statements)

References 44 publications

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“…Linear transport had speeds of 0.63-1.3 µm/s (Fig 5B right panel) that are characteristic of active motor transport and similar to the motion of growth factor complexes in anterograde and retrograde directions along neural processes [8], [37], [39], [69].…”

Section: Resultsmentioning

confidence: 81%

Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

et al. 2014

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Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide understanding of how the molecular mechanisms underlying intracellular ligand-receptor trafficking shape cell signaling under conditions of both healthy and dysfunctional neurological disease models.

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Section: Resultsmentioning

confidence: 81%

Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

et al. 2014

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“…This might be attributed to surface property and particle size of the nanospheres. It was reported that QD-loaded nanoparticles were internalized into PC12 cells via nanoparticle endocytosis, particularly via tyrosine kinase A receptor in differentiated PC12 cells [28]. In that study, the QDs modified with protein showed smaller particle size than QD-loaded nanoparticles leading to higher levels of nanoparticle endocytosis compared to the QD-loaded nanoparticles.…”

Section: Confocal Laser Scanning Microscopic Studymentioning

confidence: 84%

In vivo NIR imaging with CdTe/CdSe quantum dots entrapped in PLGA nanospheres

Kim

Cho

Trần

et al. 2011

Journal of Colloid and Interface Science

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“…As mentioned in section 6.1.3, single-molecule receptor trafficking experiments are increasingly being performed in studies employing one color of nanocrystal, and have already provided an improved understating of numerous dynamic cellular processes. 131,145,147 The application of multiple color nanocrystals, each targeted to different cellular components, to these types of dynamic imaging experiments has the added promise of yielding critical information involving protein-protein interactions, cell signaling cascades and other multi-component cellular processes for durations inaccessible to even the best organic dyes. Additionally, the development of improved surface chemistries will continue to build upon an already highly modular nanoscaffold design, facilitating efficient interrogation of any desired cellular target.…”

Section: Future Directions For Nanocrystal-based Biological Assaysmentioning

confidence: 99%

Synthesis, surface studies, composition and structural characterization of CdSe, core/shell and biologically active nanocrystals

Rosenthal

McBride

Pennycook

et al. 2007

Surface Science Reports

211

209

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Nanostructures, with their very large surface to volume ratio and their non-planar geometry, present an important challenge to surface scientists. New issues arise as to surface characterization, quantification and interface formation. This review summarizes the current state of the art in the synthesis, composition, surface and interface control of CdSe nanocrystal systems, one of the most studied and useful nanostructures. KeywordsCadmium; Selenium; Selenide; CdSe; nanocrystal; quantum dot; nanoparticle; surface; synthesis; electron microscopy; Z-STEM; RBS; alloy; core/shell; fluorescence; quantum yield; growth mechanism; expitaxy; spectroscopy 1.0 Introduction BackgroundWe are currently witnessing an explosion of research in nanoscale science, engineering, and biotechnology. As the nano-revolution proceeds, basic research is leading to the development of true nanotechnologies which have the potential to impact fields from health care and opto-electronics to energy and the environment. One particular type of nanostructure, semiconductor nanocrystals (also known as quantum dots), may ultimately be employed in technologies in each of these fields. For example, antibody-conjugated CdSe/ ZnS core-shell nanocrystals have been used to detect respiratory syncytial virus. 1 The high brightness of the quantum dots enables the virus to be detected in a matter of minutes, whereas the previous assay required 4 days. The ramification of this new technology is that anti-viral drugs can be given early in the infection when they are most effective, reducing Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptSurf Sci Rep. Author manuscript; available in PMC 2011 April 6. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript hospitalizations and deaths. In the field of opto-electronics CdSe nanocrystals have been incorporated in light emitting diodes2 -6 and it has been demonstrated that they can serve as the gain media in a laser.7 , 8 Nanocrystals are also poised to play a role in solar energy conversion.9 -14 A specific example is a device in which elongated CdSe nanocrystals (nanorods) are mixed with a conducting polymer and sandwiched between aluminum and indium tin oxide electrodes to create a device with a power conversion efficiency of 1.7 %. 12 Nanocrystals may also have a positive impact on the environment, as it has been shown that they can be used to sequester CO 2 . 15 The spark that ignited two decades of intense research in nanocrystal synthesis, properties, and applications was Louis Brus' demonstration that qua...

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Quantum Dots Monitor TrkA Receptor Dynamics in the Interior of Neural PC12 Cells

Cited by 62 publications

References 44 publications

Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

Heterogeneous Intracellular Trafficking Dynamics of Brain-Derived Neurotrophic Factor Complexes in the Neuronal Soma Revealed by Single Quantum Dot Tracking

In vivo NIR imaging with CdTe/CdSe quantum dots entrapped in PLGA nanospheres

Synthesis, surface studies, composition and structural characterization of CdSe, core/shell and biologically active nanocrystals

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