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Adam Engler, UC San Diego
Jacobs School of Engineering
The stiffness of the extracellular matrix may play a larger role in stem cell differentiation than we thought, according to a new study.
Scientists have recently suggested that protein tethering and matrix porosity, as well as matrix stiffness and ligand type, regulate stem cell differentiation.
However, new research published in Nature Materials indicates that matrix stiffness regulates stem cell differentiation independently of tethering and porosity.
Adam Engler, PhD, of the University of California, San Diego, and his colleagues discovered that human adipose stromal cells and mesenchymal stromal cells underwent osteogenic differentiation if placed in a stiff hydrogel. But the cells underwent adipogenesis if placed in a soft hydrogel.
The protein binding the stem cell to the hydrogel was not a factor in the differentiation process. Results suggested the protein layer was merely an adhesive.
The researchers found that stem cell differentiation is a response to the mechanical deformation of the hydrogel from the force exerted by the cell. With a series of experiments, the team showed that this happens whether the protein tethering the cell to the matrix is tight, loose, or nonexistent.
Across multiple samples using a stiff matrix, varying the degree of tethering made no significant difference in the rate of osteogenic or adipogenic differentiation.
Likewise, the size of the pores in the matrix had no effect on stem cell differentiation, as long as the stiffness of the hydrogel remained the same.
However, Dr Engler pointed out that matrix stiffness is only “one cue out of dozens that are important in stem cell differentiation.”
“That doesn’t mean the other cues are irrelevant,” he noted. “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.” 
Adam Engler, UC San Diego
Jacobs School of Engineering
The stiffness of the extracellular matrix may play a larger role in stem cell differentiation than we thought, according to a new study.
Scientists have recently suggested that protein tethering and matrix porosity, as well as matrix stiffness and ligand type, regulate stem cell differentiation.
However, new research published in Nature Materials indicates that matrix stiffness regulates stem cell differentiation independently of tethering and porosity.
Adam Engler, PhD, of the University of California, San Diego, and his colleagues discovered that human adipose stromal cells and mesenchymal stromal cells underwent osteogenic differentiation if placed in a stiff hydrogel. But the cells underwent adipogenesis if placed in a soft hydrogel.
The protein binding the stem cell to the hydrogel was not a factor in the differentiation process. Results suggested the protein layer was merely an adhesive.
The researchers found that stem cell differentiation is a response to the mechanical deformation of the hydrogel from the force exerted by the cell. With a series of experiments, the team showed that this happens whether the protein tethering the cell to the matrix is tight, loose, or nonexistent.
Across multiple samples using a stiff matrix, varying the degree of tethering made no significant difference in the rate of osteogenic or adipogenic differentiation.
Likewise, the size of the pores in the matrix had no effect on stem cell differentiation, as long as the stiffness of the hydrogel remained the same.
However, Dr Engler pointed out that matrix stiffness is only “one cue out of dozens that are important in stem cell differentiation.”
“That doesn’t mean the other cues are irrelevant,” he noted. “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.”
Adam Engler, UC San Diego
Jacobs School of Engineering
The stiffness of the extracellular matrix may play a larger role in stem cell differentiation than we thought, according to a new study.
Scientists have recently suggested that protein tethering and matrix porosity, as well as matrix stiffness and ligand type, regulate stem cell differentiation.
However, new research published in Nature Materials indicates that matrix stiffness regulates stem cell differentiation independently of tethering and porosity.
Adam Engler, PhD, of the University of California, San Diego, and his colleagues discovered that human adipose stromal cells and mesenchymal stromal cells underwent osteogenic differentiation if placed in a stiff hydrogel. But the cells underwent adipogenesis if placed in a soft hydrogel.
The protein binding the stem cell to the hydrogel was not a factor in the differentiation process. Results suggested the protein layer was merely an adhesive.
The researchers found that stem cell differentiation is a response to the mechanical deformation of the hydrogel from the force exerted by the cell. With a series of experiments, the team showed that this happens whether the protein tethering the cell to the matrix is tight, loose, or nonexistent.
Across multiple samples using a stiff matrix, varying the degree of tethering made no significant difference in the rate of osteogenic or adipogenic differentiation.
Likewise, the size of the pores in the matrix had no effect on stem cell differentiation, as long as the stiffness of the hydrogel remained the same.
However, Dr Engler pointed out that matrix stiffness is only “one cue out of dozens that are important in stem cell differentiation.”
“That doesn’t mean the other cues are irrelevant,” he noted. “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.”