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Nearest neighbor analysis of dopamine D1 receptors and Na plus -K plus -ATPases in dendritic spines dissected by STED microscopy
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.ORCID iD: 0000-0002-5584-9170
KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
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2012 (English)In: Microscopy research and technique (Print), ISSN 1059-910X, E-ISSN 1097-0029, Vol. 75, no 2, 220-228 p.Article in journal (Refereed) Published
Abstract [en]

Protein localization in dendritic spines is the focus of intense investigations within neuroscience. Applications of super-resolution microscopy to dissect nanoscale protein distributions, as shown in this work with dual-color STED, generate spatial correlation coefficients having quite small values. This means that colocalization analysis to some extent looses part of its correlative impact. In this study we thus introduced nearest neighbor analysis to quantify the spatial relations between two important proteins in neurons, the dopamine D1 receptor and Na+,K+-ATPase. The analysis gave new information on how dense the D1 receptor and Na+,K+-ATPase constituting nanoclusters are located both with respect to the homogenous (self to same) and the heterogeneous (same to other) topology. The STED dissected nanoscale topologies provide evidence for both a joint as well as a separated confinement of the D1 receptor and the Na+,K+-ATPase in the postsynaptic areas of dendritic spines. This confined topology may have implications for generation of local sodium gradients and for structural and functional interactions modulating slow synaptic transmission processes. Microsc. Res. Tech., 2011.

Place, publisher, year, edition, pages
2012. Vol. 75, no 2, 220-228 p.
Keyword [en]
fluorescence microscopy, STED, localization, striatal neurons
National Category
Medical Biotechnology
URN: urn:nbn:se:kth:diva-50744DOI: 10.1002/jemt.21046ISI: 000299208300016ScopusID: 2-s2.0-84856004577OAI: diva2:462588
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research Council, VR-2006-3197 VR-2007-4582 VR-2007-2519Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 20120309Available from: 2011-12-07 Created: 2011-12-07 Last updated: 2014-02-07Bibliographically approved
In thesis
1. Super resolution optical imaging – image analysis, multicolor development and biological applications
Open this publication in new window or tab >>Super resolution optical imaging – image analysis, multicolor development and biological applications
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis focuses on super resolution STED optical imaging. STED provides a wealth of new informational content to the acquired images by using stimulated emission to surpass the diffraction limit in optical fluorescence microscopy. To further increase the informational content, a new method to perform multicolor STED imaging by exploiting differences in the photostability and excitation spectra of dyes is presented. In order to extract information from the images, computational algorithms which handle the new type of high resolution informational content are developed.

We propose that multicolor super resolution imaging in combination with image analysis can reduce the amount of clinical samples required to perform accurate cancer diagnosis. To date, such diagnosis is based mainly on significant amounts of tissue samples extracted from the suspected tumor site. The sample extraction often requires anesthetics and can lead to complications such as hematoma, infections and even cancer cell ceding along the needle track. We show that by applying multicolor STED and image analysis, the information gained from single cells is greatly increased. We therefore propose that accurate diagnosis can be based on significantly less extracted tissue material, allowing for a more patient friendly sampling. This approach can also be applied when studying blood platelets, where we show how the high informational content can be used to identify platelet specific activational states. Since platelets are involved in many different types of diseases, such analysis could provide means of performing truly minimally invasive diagnostics based on a simple blood test.

In addition, our data makes it possible to understand in finer detail the underlying mechanisms rendering cells metastasis competent. We combine the high resolution spatial information provided by STED with information regarding the adhesive forces of cells measured by TFM (Traction Force Microscopy) and the cell stiffness measured by AFM (Atomic Force Microscopy). Such comparisons provide a link between the specific highly resolved protein distributions and different cellular mechanics and functions.

This thesis also includes STED imaging and analysis on the spatial organization of neuronal synaptic regulating proteins, implicating the speed with which neuronal signaling can be regulated.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2014. x, 86 p.
TRITA-FYS, ISSN 0280-316X ; 2014:04
Stimulated emission depletion (STED) microscopy, nanoscopy, multicolor, image analysis, diagnostics, cancer, metastasis
National Category
Physical Sciences
Research subject
Biological Physics
urn:nbn:se:kth:diva-141011 (URN)978-91-7595-001-3 (ISBN)
Public defence
2014-02-28, FB42, AlbaNova Universitetscentrum, Roslagstullsbacken 21, Stockholm, 10:51 (English)

QC 20140207

Available from: 2014-02-07 Created: 2014-02-05 Last updated: 2014-02-07Bibliographically approved

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Blom, HansRönnlund, DanielWidengren, JerkerBrismar, Hjalmar
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