Oct 13, 2014 Stem cells show auxeticity; the nucleus expands, rather than thins, when it's stretched. Credit: Effigos AG

Looking at stem cells through physicists' eyes is challenging some of our basic assumptions about the body's master cells.

One of the many mysteries surrounding stem cells is how the constantly regenerating cells in adults, such as those in skin, are able to achieve the delicate balance between self-renewal and differentiation in other words, both maintaining their numbers and producing cells that are more specialised to replace those that are used up or damaged.

"What all of us want to understand is how stem cells decide to make and maintain a body plan," said Dr Kevin Chalut, a Cambridge physicist who moved his lab to the University's Wellcome Trust-MRC Cambridge Stem Cell Institute two years ago. "How do they decide whether they're going to differentiate or stay a stem cell in order to replenish tissue? We have discovered a lot about stem cells, but at this point nobody can tell you exactly how they maintain that balance."

To unravel this mystery, both Chalut and another physicist, Professor Ben Simons, are bringing a fresh perspective to the biologists' work. Looking at problems through the lens of a physicist helps them untangle many of the complex datasets associated with stem cell research. It also, they say, makes them unafraid to ask questions that some biologists might consider 'heretical', such as whether a few simple rules describe stem cells. "As physicists, we're very used to the idea that complex systems have emergent behaviour that may be described by simple rules," explained Simons.

What they have discovered is challenging some of the basic assumptions we have about stem cells.

One of those assumptions is that once a stem cell has been 'fated' for differentiation, there's no going back. "In fact, it appears that stem cells are much more adaptable than previously thought," said Simons.

By using fluorescent markers and live imaging to track a stem cell's progression, Simons' group has found that they can move backwards and forwards between states biased towards renewal and differentiation, depending on their physical position in the their host environment, known as the stem cell niche.

For example, some have argued that mammals, from elephants to mice, require just a few hundred blood stem cells to maintain sufficient levels of blood in the body. "Which sounds crazy," said Simons. "But if the self-renewal potential of cells may vary reversibly, the number of cells that retain stem cell potential may be much higher. Just because a certain cell may have a low chance of self-renewal today doesn't mean that it will still be low tomorrow or next week!"

Chalut's group is also looking at the way in which stem cells interact with their environment, specifically at the role that their physical and mechanical properties might play in how they make their fate decisions. It's a little-studied area, but one that could play a key role in understanding how stem cells work.

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