Jostling spurs cell spreading

Tiny physical pokes and prods may be enough to spur stem cell movement and differentiation, according to a new study published online in Nature Materials today (October 18). These findings suggest mechanical forces in the early embryo's microenvironment may play a bigger role in its development than scientists had realized.

By | October 18, 2009

Tiny physical pokes and prods may be enough to spur stem cell movement and differentiation, according to a new study published online in Nature Materials today (October 18). These findings suggest mechanical forces in the early embryo's microenvironment may play a bigger role in its development than scientists had realized.
A soft embryonic stem cell (left)
has a large nucleus (blue) and
relatively little actin (red) and
responds to applied stress by
spreading and downregulating
gene expression; stiff
differentiated cells (right)
have more actin bundles and
do not respond to applied stress.

Image: F.Chowdhury/N.Wang
"I think it is very exciting work," Harvard University cell biologist linkurl:Donald Ingber,; who was not involved in the research, wrote in an email to The Scientist. "It further goes to show the fundamental role that mechanical forces play in development control." Previous research has shown that stretching or stressing a whole cell can elongate the cell in the direction of the stress, but how cells would respond to relatively small and localized external forces was unclear. Bioengineer linkurl:Ning Wang; of the University of Illinois at Urbana-Champaign and his colleagues carefully attached a ligand-coated bead to a focal adhesion -- a complex on the cell surface that binds it to the extracellular matrix. They then used a magnetic field to gently push and pull on the bead, a technique known as magnetic twisting cytometry. Within 30 seconds of applying the force, mouse embryonic stem (mES) cells began spreading across the substrate. mES cell-differentiated (ESD) cells, however, did not seem to respond at all. "We were so surprised," Wang said. "Every time we give a little bit of force, [the ES cells] start to spread, [but] then we look at differentiated cells, and they don't do that." It turns out that mES cells are 10 times softer than ESD cells. The softness of a cell is determined primarily by the size and structure of the cell's cytoskeleton. Specifically, the polymerization of F-actin bundles during focal adhesion formation stiffens the cells. When the researchers artificially softened the ESD cells by growing them on a substrate only sparsely coated with the proteins needed to support the generation of actin bundles, the cells started to spread in response to the localized stress. "It's really how soft the cell is [that] will dictate how sensitive cells will be to local force," Wang said. "[Because ES] cells are so soft, they are so sensitive to force." Thus, small local forces, such as those inflicted by neighboring cells in the growing embryo, may be active players in development. In addition to spreading, the local stress appeared to initiate differentiation in mES cells, as measured by the downregulation of oct3/4 expression -- a common marker of undifferentiated cells. Twenty-four hours after 60 minutes of force application, oct3/4 expression had dropped by 35%, and 48 hours later was down to 50% of its original levels. Unmanipulated cells just micrometers away in the same dish, however, continued to express oct3/4, suggesting that physical deformation of cells may be a cell-specific way to induce differentiation. "There's a ways to go," Wang admitted, "but certainly this is opening new directions." Understanding the mechanism underlying these changes, and determining what types of mechanical perturbations can cause differentiation into which cell types, are next on Wang's to do list. "It takes large steps forward toward [understanding] development as well as stem cell application," linkurl:Dennis Discher; of the University of Pennsylvania, who did not contribute to the research, said in an email. "It will no doubt inspire a lot more work on various types of stem cells."
**__Related stories:__***linkurl:Stem cells model disease;
[14th November 2007]*linkurl:Making Sense of Mechanosensation;
[10th May 2004]*linkurl:Stem Cell Potential Grows;
[2nd September 2002]


Avatar of: anonymous poster

anonymous poster

Posts: 85

October 19, 2009

There are some scientists out there who won't find these results particularly surprising (such as Don Ingber, who was quoted in the article, or Mina Bissell, just to name two out of a very large handful of "mavericks" in cell biology and developmental biology who have been trying to push the conceptual envelope in this direction for some time now). I'm pleased to see that the ideas are getting some much-needed publicity, but I do dearly hope that all of the creative and persistent investigators who have been working in this area, some of them for decades, will finally get appropriate due credit for the paths they've trailblazed. Some of them have persevered despite encountering considerable obstacles in getting their work supported through mainstream sources of funding such as NIH, largely because their work has been so envelope-pushing and so contrary to what until now has been considered "that which is already known." These scientists deserve their recognition! \n\nAnd -- study section members PLEASE take note -- just because something doesn't fit the current dogma doesn't mean it isn't worth pursuing!! Please consider the possibility that it may be far more worthwhile to pursue the unknown than to pursue the already-known!
Avatar of: Dov Henis

Dov Henis

Posts: 97

October 21, 2009

Genostemness Induction By Mechanical Force\n\nIn "Genostemness Induction"\n\n\nsee\n\nFrom "For blood stem cells, the force is strong" \n \nBlood flow boosts production of blood stem cells, two new studies show.\n\n"It?s still not clear how the cells sense shear stress, and researchers are trying to unravel the chain of events between mechanical force and stem cell production in order to manipulate the process to make blood stem cells for transplant."\n\n\nDov Henis
Avatar of: anonymous poster

anonymous poster

Posts: 1

November 17, 2009

Perhaps the jostling of embryonic cells during common fetal ultrasounds may not be totally benign, then?\nAlso, could this be a way to force cancer stem cells to differentiate and thus lose their malignancy?\nJust thoughts ...

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