Bioengineers at the University of California, San Diego have proven that when it comes to guiding stem cells into a specific cell type, the stiffness of the extracellular matrix used to culture them really does matter.
When placed in a dish of a very stiff material, or hydrogel, most stem cells become bone-like cells. By comparison, soft materials tend to steer stem cells into soft tissues such as neurons and fat cells.
Cells grown on hydrogels of the same stiffness all display fat cell markers and deform the underlying matrix material the same way.
Credit: Adam Engler, UC San Diego Jacobs School of Engineering
The research team, led by bioengineering professor Adam Engler, also found that a protein binding the stem cell to the hydrogel is not a factor in the differentiation of the stem cell as previously suggested. The protein layer is merely an adhesive, the team reported Aug. 10 in the advance online edition of the journal Nature Materials.
Their findings affirm Engler's prior work on the relationship between matrix stiffness and stem cell differentiations.
"What's remarkable is that you can see that the cells have made the first decisions to become bone cells, with just this one cue. That's why this is important for tissue engineering," said Engler, a professor at the UC San Diego Jacobs School of Engineering.
Engler's team, which includes bioengineering graduate student researchers Ludovic Vincent and Jessica Wen, found that the stem cell differentiation is a response to the mechanical deformation of the hydrogel from the force exerted by the cell.
In a series of experiments, the team found that this happens whether the protein tethering the cell to the matrix is tight, loose or nonexistent. To illustrate the concept, Vincent described the pores in the matrix as holes in a sponge covered with ropes of protein fibers.
Imagine that a rope is draped over a number of these holes, tethered loosely with only a few anchors or tightly with many anchors. Across multiple samples using a stiff matrix, while varying the degree of tethering, the researchers found no difference in the rate at which stem cells showed signs of turning into bone-like cells.
The team also found that the size of the pores in the matrix also had no effect on the differentiation of the stem cells as long as the stiffness of the hydrogel remained the same.
"We made the stiffness the same and changed how the protein is presented to the cells (by varying the size of the pores and tethering) and ask whether or not the cells change their behavior," Vincent said. "Do they respond only to the stiffness? Neither the tethering nor the pore size changed the cells."
"We're only giving them one cue out of dozens that are important in stem cell differentiation," said Engler. "That doesn't mean the other cues are irrelevant; they may still push the cells into a specific cell type. We have just ruled out porosity and tethering, and further emphasized stiffness in this process."
The paper is "Interplay of matrix stiffness and protein tethering in stem cell differentiation," by Jessica H. Wen, Ludovic G. Vincent, Alexander Fuhrmann, Yu Suk Choi, Kolin Hribar, Hermes Taylor-Weiner, Shaochen Chen and Adam J. Engler in the Departments of Bioengineering and NanoEngineering at UC San Diego Jacobs School of Engineering. Engler is also a researcher at the Sanford Consortium for Regenerative Medicine. His work is partially funded by the National Institutes of Health (DP02D006460).
Catherine Hockmuth | Eurek Alert!
MACC1 Gene Is an Independent Prognostic Biomarker for Survival in Klatskin Tumor Patients
31.08.2015 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft
Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from University of Arizona geoscientists. The study is the first to explain how the steep-fronted plateau formed.
China's Loess Plateau was formed by wind alternately depositing dust or removing dust over the last 2.6 million years, according to a new report from...
The leaves of the lotus flower, and other natural surfaces that repel water and dirt, have been the model for many types of engineered liquid-repelling surfaces. As slippery as these surfaces are, however, tiny water droplets still stick to them. Now, Penn State researchers have developed nano/micro-textured, highly slippery surfaces able to outperform these naturally inspired coatings, particularly when the water is a vapor or tiny droplets.
Enhancing the mobility of liquid droplets on rough surfaces could improve condensation heat transfer for power-plant heat exchangers, create more efficient...
Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.
"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...
A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.
The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...
A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).
Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...
20.08.2015 | Event News
20.08.2015 | Event News
19.08.2015 | Event News
02.09.2015 | Earth Sciences
02.09.2015 | Studies and Analyses
01.09.2015 | Press release