Researchers at Columbia University have reported a new approach to visualize glucose uptake activity in single living cells by light microscopy with minimum disturbance. In a recent study published in Angewandte Chemie International Edition , Associate Professor of Chemistry Wei Min's team developed a new glucose analogue that can mimic the natural glucose, and imaged its uptake as energy source by living cancer cells, neurons and tissues at the single cell level.
Glucose is consumed as an energy source by almost all life forms, from bacteria to human. The uptake of glucose by cells closely reflects their energetic needs, and is becoming poorly regulated in many pathological conditions such as obesity, diabetes and cancer. To visualize this important process, several prominent techniques have been developed in the past few decades.
Radioactive fluorine-18 labeled glucose FDG is widely applied in clinical cancer diagnostics to locate metabolic hot spots in human body using positron emission tomography (PET). Magnetic resonance imaging (MRI) has recently demonstrated glucose imaging in mouse tumors. Although both methods find great use in clinical application, they do not have sufficient spatial resolution to visualize glucose uptake down to single cells.
To image glucose uptake activity at the cellular level, glucose analogues labeled with fluorescent dyes have been developed. Unfortunately, tagging fluorophores onto glucose alters its chemical property. Moreover, fluorescent dyes are always larger than the glucose itself. Therefore, most fluorescent glucose analogues have undesired interactions in cells and tissues, which would bias the true glucose distribution.
To overcome these problems, Min and his team developed a new modality to visualize glucose uptake activity inside single cells based on stimulated Raman scattering (SRS) imaging, and demonstrated its use in live cancer cells, tumor xenograft tissues, primary neurons and mouse brain tissues. Coupling SRS with alkyne tags has been reported earlier by the same group as a general strategy for imaging small biomolecules .
Specifically, glucose is labeled with a small alkyne tag (i.e., carbon-carbon triple bond) to generate a strong and characteristic Raman scattering signal in the otherwise silent region, which can be picked up by SRS microscope with high sensitivity and specificity to produce a quantitative concentration map in three dimensions.
This technique is able to distinguish cancer cell lines with differing metabolic activities and reveals heterogeneous uptake patterns in neurons, mouse brain tissues and tumor tissues with clear cell-to-cell variations. The border between tumor proliferating region and the necrotic region can be clearly visualized down to single cell with sharp contrast in glucose uptake activity.
"By offering the distinct advantage of subcellular resolution and avoiding the undesirable influence of fluorescent dyes, we believe our technique can complement FDG in clinical PET imaging for visualizing glucose uptake activity at the cellular level", says the lead author Fanghao Hu, a Ph.D. candidate in chemistry. Currently, Min's team is working on applying this technique for imaging glucose uptake dynamics in mice.
"We expect that our new method will become an attractive tool to study energy requirements of living systems with subcellular resolution", says Min, "especially in brain and malignant tumors that are in high demand of energy."
Wei Min | EurekAlert!
Researchers show p300 protein may suppress leukemia in MDS patients
28.03.2017 | University of Miami Miller School of Medicine
When writing interferes with hearing
28.03.2017 | Université de Genève
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Physics and Astronomy
28.03.2017 | Health and Medicine
28.03.2017 | Life Sciences