Matrix stiffness is an essential tool in stem cell differentiation, bioengineers report

August 10, 2014
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

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. 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 and stem cell differentiations.

"What's remarkable is that you can see that the cells have made the first decisions to become , 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 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 as long as the stiffness of the hydrogel remained the same.

Cells grown on three hydrogels of the same stiffness all display fat cell markers and deform the underlying matrix material in the same way. Credit: Adam Engler, UC San Diego Jacobs School of Engineering

"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."

Cells grown on three hydrogels of the same stiffness all display fat cell markers and deform the underlying matrix material in the same way. Credit: Adam Engler/UC San Diego Jacobs School of Engineering

"We're only giving them one cue out of dozens that are important in stem ," 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."

Explore further: Development of 'matrix' material controlling differentiation of stem cells

More information: Interplay of matrix stiffness and protein tethering in stem cell differentiation, Nature Materials, DOI: 10.1038/nmat4051

Related Stories

Need muscle for a tough spot? Turn to fat stem cells

January 27, 2012

( -- Stem cells derived from fat have a surprising trick up their sleeves: Encouraged to develop on a stiff surface, they undergo a remarkable transformation toward becoming mature muscle cells. The new research ...

New biomaterial gets 'sticky' with stem cells

December 10, 2012

(—Just like the bones that hold up your body, your cells have their own scaffolding that holds them up. This scaffolding, known as the extracellular matrix, or ECM, not only props up cells but also provides attachment ...

Researchers find stem cells remember prior substrates

March 17, 2014

( —A team of researchers working at the University of Colorado has found that human stem cells appear to remember the physical nature of the structure they were grown on, after being moved to a different substrate. ...

Recommended for you

New gene map reveals cancer's Achilles heel

November 25, 2015

Scientists have mapped out the genes that keep our cells alive, creating a long-awaited foothold for understanding how our genome works and which genes are crucial in disease like cancer.

Study suggests fish can experience 'emotional fever'

November 25, 2015

(—A small team of researchers from the U.K. and Spain has found via lab study that at least one type of fish is capable of experiencing 'emotional fever,' which suggests it may qualify as a sentient being. In their ...

How cells in the developing ear 'practice' hearing

November 25, 2015

Before the fluid of the middle ear drains and sound waves penetrate for the first time, the inner ear cells of newborn rodents practice for their big debut. Researchers at Johns Hopkins report they have figured out the molecular ...

How cells 'climb' to build fruit fly tracheas

November 25, 2015

Fruit fly windpipes are much more like human blood vessels than the entryway to human lungs. To create that intricate network, fly embryonic cells must sprout "fingers" and crawl into place. Now researchers at The Johns Hopkins ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.