To create drugs capable of targeting some of the most devastating human diseases, scientists must first decode exactly how a cell or a group of cells communicates with other cells and reacts to a broad spectrum of complex biomolecules surrounding it.
But even the most sophisticated tools currently used for studying cell communications suffer from significant deficiencies. Typically, these tools can detect only a narrowly selected group of small molecules or, for a more sophisticated analysis, the cells must be destroyed for sample preparation. This makes it very difficult to observe complex cellular interactions just as they would occur in their natural habitat — the human body.
Georgia Tech researchers have created a nanoscale probe, the Scanning Mass Spectrometry (SMS) probe, that can capture both the biochemical makeup and topography of complex biological objects in their normal environment — opening the door for discovery of new biomarkers and improved gene studies, leading to better disease diagnosis and drug design on the cellular level. The research was presented in the July issue of IEE Electronics Letters.
The new instrument, a potentially very valuable tool for the emerging science of systems biology, may help researchers better understand cellular interactions at the most fundamental level, including cell signaling, as well as identifying protein expression and response to the external stimuli (e.g., exposure to drugs or changes in the environment) from the organ scale down to tissue and even the single cell level.
“At its core, disease is a disruption of normal cell signaling,” said Dr. Andrei Fedorov, a professor in Georgia Tech’s Woodruff School of Mechanical Engineering and lead researcher on the project. “So, if one understands the network and all signals on the most fundamental level, one would be able to control and correct them if needed. The SMS probe can help map all those complex and intricate cellular communication pathways by probing cell activities in the natural cellular environment.”
The SMS probe offers the capability to gently pull biomolecules (proteins, metabolites, peptides) precisely at a specific point on the cell/tissue surface, ionize these biomolecules and produce “dry” ions suitable for analysis and then transport those ions to the mass spectrometer (an instrument that can detect proteins present even in ultra-small concentrations by measuring the relative masses of ionized atoms and molecules) for identification. The probe does this dynamically (not statically), imaging the surface and mapping cellular activities and communication potentially in real time. In essence, in scanning mode, the SMS probe could create images similar to movies of cell biochemical activities with high spatial and temporal resolution.
The SMS probe can be readily integrated with the Atomic Force Microscope (AFM) or other scanning probes, and can not only image biochemical activity but also monitor the changes in the cell/tissue topology during the imaging.
“The probe potentially allows us to detect complex mechano-bio-electro-chemical events underlying cell communication, all at the same time!” Fedorov said. “The future work is in refinement of the idea and development of a versatile instrument that can be used by biological and medical scientists in advancing the frontiers of biomedical research.”
The key challenge for the Georgia Tech team, which includes Dr. Levent Degertekin, was to create a way for a mass spectrometer, the primary tool for studying proteins, to sample biomolecules from a small domain and do it dynamically, thus enabling biochemical imaging. The researchers had to find a way to pull the targeted molecules out of the sample, as if they were using virtual tweezers, and then transfer these molecules into a dry and electrically charged state suitable for mass spectrometric analysis.
The solution to the problem came from a trick related to the basic fluid mechanics of ionic fluids, as the researchers exploited strong capillary forces to confine fluid within a nanoscale domain of the probe inlet (enabling natural separation of liquid and gaseous environments) and then used the classical Taylor electrohydrodynamic focusing of the jets to produce charged ions, but in reverse (pull) rather than in a commonly-used forward (push) mode.
The Georgia Institute of Technology is one of the nation's premiere research universities. Ranked ninth among U.S. News & World Report's top public universities, Georgia Tech educates more than 17,000 students every year through its Colleges of Architecture, Computing, Engineering, Liberal Arts, Management and Sciences. Tech maintains a diverse campus and is among the nation's top producers of women and African-American engineers. The Institute offers research opportunities to both undergraduate and graduate students and is home to more than 100 interdisciplinary units plus the Georgia Tech Research Institute. During the 2004-2005 academic year, Georgia Tech reached $357 million in new research award funding. The Institute also maintains an international presence with campuses in France and Singapore and partnerships throughout the world.
Megan McRainey | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
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...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy