[GRG] Matrix stiffness is an essential tool in stem cell differentiation


Contact: Catherine Hockmuth
University of California – San Diego

Bioengineers: Matrix stiffness is an essential tool in stem cell

IMAGE: Cells grown on hydrogels of the same stiffness all display
fat cell markers and deform the underlying matrix material the same

Click here for more information.

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.

IMAGE: Cells grown on three hydrogels of the same stiffness all
display fat cell markers and deform the underlying matrix material
in the same way.

Click here for more information.

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.

IMAGE: Cells grown on three hydrogels of the same stiffness all
display fat cell markers and deform the underlying matrix material
in the same way.

Click here for more information.

“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).

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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