Biologists tend to look at cells in bulk, observing them as a group and taking the average behavior as the norm — the assumption is that genetically identical cells all behave the same way.
In a paper to be published in the online Early Edition of Proceedings of the National Academy of Sciences the week of March 7, 2011, Sam Sia, assistant professor of biomedical engineering at Columbia Engineering, presents the results of his four-year tissue-engineering study that show a surprising range of variation in how individual cells behave during formation of a blood vessel.
Sia and his team used a new method to painstakingly observe and track individual behaviors, characterizing, for the first time, what happens when human endothelial cells move from an initial dispersed state to the formation of capillary-like structures.
"We were really surprised by this behavior," says Sia, who was named one of the world's top young innovators for 2010 by MIT's Technology Review for his work in biotechnology and medicine. "In contrast to the population-averaged behavior that most studies report, most individual cells followed distinct patterns of cell-shape changes that were not reflected in the bulk average."
This is one of the first explicit studies to look at the variations between cells during tissue formation, and overturns the assumption that genetically identical cells behave in generally similar ways. Using a systematic approach to quantifying the changes in cell shape and movement for every single endothelial cell over time, the Columbia Engineering team found unexpected hidden patterns in behavior. In addition to discovering that most cells behave differently from the average, the team also observed that groups of cells behaved in similar fashions, and that some of these clusters of behavior resulted in distinct structural roles in the final blood-vessel network.
The origins of the variations in behavior are not known right now. Sia notes that "one possibility is simply random noise or naturally occurring fluctuations, which have been shown by other researchers to be important in producing biologically significant variations in gene expression and other subcellular processes. It's also possible there are subtle local variations in the extracellular environment that we're not aware of yet."
Sia says an application of this work is to exploit his technique to identify new drugs that modify angiogenesis. "A lot of drugs that either help or hinder blood-vessel formation have unknown mechanisms. This technique can potentially unravel some of those mechanisms, and help identify compounds that modulate specific aspects of how blood vessels form." In addition, knowledge of how individual cells behave will help in high-precision tissue engineering, an ongoing field of research in Sia's lab. "Knowledge of how individual cells or groups of cells behave enhances our understanding of how native tissues self-organize," he says. "This could ultimately enable more precise approaches for engineering complex multicellular tissues."
Sia was also named in 2010 by NASA as one of the ten innovators in human health and sustainability. In 2008, he received a CAREER award from the National Science Foundation that included a $400,000 grant to support his other research specialty in three-dimensional tissue engineering. A recipient of the Walter H. Coulter Early Career Award in 2008, Sia participated in the National Academy of Engineering's U.S. Frontiers of Engineering symposium for the nation's brightest young engineers in 2007.
His research is focused on developing new high-resolution tools to control the extracellular environments around cells, in order to study how they interact to form human tissues and organs. His lab uses techniques from a number of different fields, including biochemistry, molecular biology, microfabrication, microfluidics, materials chemistry, and cell and tissue biology.
Sia earned his B.Sc. in biochemistry from the University of Alberta, and his Ph.D. in biophysics from Harvard University, where he also a postdoctoral fellow in chemistry and chemical biology.
This study has been supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute) and the National Science Foundation.
Columbia University's Fu Foundation School of Engineering and Applied Science, founded in 1864, offers programs in nine departments to both undergraduate and graduate students. With facilities specifically designed and equipped to meet the laboratory and research needs of faculty and students, Columbia Engineering is home to NSF-NIH funded centers in genomic science, molecular nanostructures, materials science, and energy, as well as one of the world's leading programs in financial engineering. These interdisciplinary centers are leading the way in their respective fields while individual groups of engineers and scientists collaborate to solve some of society's more vexing challenges.
How cells hack their own genes
24.08.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy