By guest blogger Jane Cheung
With contributions from Casandra Gardner, PhD and Joanna Fromstein P.Eng (Centre for Commercialization of Regenerative Medicine)
“Fate has brought us here.”
“This is my destiny.”
We often read or hear these phrases in books or movies. Often times, as the plot goes on, the main characters will utter, “We can change our fate!” That’s when we know there’ll be a twist to the story.
In reality, can we really change our fate?
I would say yes, at least at the cellular level – the fate of our cells.
The use of genetic modification to “twist” a cell’s fate is well known; however, those who aren’t familiar with biomaterials may not realize that they are also able to manipulate cell fate. Here’s why I think biomaterials – materials that are used in biological applications – are even more interesting.
A cell’s fate is not only controlled by its surrounding chemical microenvironment (e.g. growth factors and cytokines), but also its mechanical and physical microenvironment (e.g. extracellular matrix (ECM)). The topography and stiffness (mechanical properties) of the tissue or material a cell sits on can both affect how the cell behaves. Researchers have used this knowledge and applied it to biomaterials to trick the cells, by varying the design of the biomaterial, so that it can either mimic the cells’ original home (niche), or create an entirely different place for them to begin a new life.
Biomaterials can also change cell behaviour by altering the structure of proteins that are attached to the material’s surface . Sometimes, these structural changes may expose hidden parts in the protein that can stimulate cellular events such as stem cell differentiation or even wound healing.
For example, by increasing the surface wettability of polyethylene and polypropylene (types of plastic), Dr. Robert Latour’s group, from Clemson University, greatly changes the structures of albumin and fibrinogen, which affect the way blood clots. By changing the surface properties, materials that are better candidates for vascular grafts – that might otherwise become clogged – can be designed.
Aside from protein structural changes, we can attach chemical cues (e.g. growth factor-like reagents) to biomaterials to direct stem cell fate. In a recent study by Dr. David Mooney from Harvard University, he demonstrates that by engineering a biomaterial’s surface, we can program mesenchymal stem cells to become osteoblast-like.
As I mentioned, things can get “physical” when we want to alter a cell’s fate. Cells can perceive the mechanical signals in their environment via cell membrane proteins such as integrins – the bridges for cell to cell and cell to ECM interactions. These membrane proteins translate mechanical signals into intracellular biochemical signals, a process called mechanotransduction. Mechanotransduction is a remarkable phenomenon because it can be profound and pivotal to normal physiology and even in diseases. Since the scope of mechanotransduction is vast and complex, I hereby recommend a book called “Introductory Biomechanics From Cells to Organisms,” written by Drs. Ross Ethier and Craig Simmons , for more in-depth detail.
Adding physical features (e.g. nano-ridges) to a biomaterial is one of the many ways to create mechanical signals. For example, polylactic acid micro-channels with a diameter of 200 µm can be made with a method called lithography. When sitting in these channels, nerve stem cells can sense the confinement, align themselves, and then differentiate. If you want to explore this further, there’s more information here.
Sitting on a hard vs. soft surface also makes a difference.
The stiffness of the material greatly affects a stem cell’s decision on what it should become. As published in the Cell in 2006, the work of Engler et al. has shown us that stem cells can differentiate into bone cells on hard surfaces (elastic modulus = 25-40 kPa), while on very soft surfaces (0.1-1 kPa), they can turn into brain cells, even though both surfaces are made of the same base material (collagen-coated polyacrylamide gels).
That’s not all. Things get exciting when cells experience “a twist of fate” on a biomaterial’s surface.
Myofibroblasts – a cell that is in between a fibroblast and a smooth muscle cell in differentiation – can lose their characteristic traits on soft surfaces and become typical fibroblasts. Dr. Boris Hinz, at the University of Toronto, proposed that this might be due to a release of stress in the microenvironment. Since myofibroblasts live in a stressed environment (yes, they have a stressful life) and are sensitive to surrounding stresses, the soft surface reduces the amount of stress on the cell membrane, which triggers a canonical series of intracellular events leading to cell behavioural changes. You can learn more about Dr. Hinz’s study here.
Image: Stiffness of a biomaterial can change a cell’s fate. (Left) typical fibroblasts on soft surface, (middle) fibroblasts becoming myofibroblast-like on medium stiff surface, (right) fibroblasts differentiate into myofibroblasts on stiff surface. Adapted from Hinz et al. (http://www.ncbi.nlm.nih.gov/pubmed/17299435).
These are just some examples of how we can fiddle around with biomaterials to direct cell behaviour. A lot of current research is exploring new ways of using biomaterials for this purpose.
If you weren’t already a biomaterials devotee, I hope I’ve convinced you that biomaterials can be modified using a wide variety of techniques to become cell fate-twisters. Above all, we should appreciate the diversity and complexity of biomaterial design.
 Sarkar D, Ankrum JA, Teo GSL, Carman CV, Karp JM. Cellular and extracellular programming of cell fate through engineered intracrine-, paracrine-, and endocrine-like mechanisms. Biomaterials. 2011;32:3053-61.
 Ethier CR and Simmons CA. Introductory Biomechanics From Cells to Organisms. New York: Cambridge University Press, 2007.
Jane is a PhD student at the Institute of Biomaterials and Biomedical Engineering at the University of Toronto. Her research focuses on gingival tissue engineering using degradable polyurethane scaffolds and a custom-designed perfusion system. She will be gaining her degree this month (March 2015). Her research work was recently published in Tissue Engineering Part A (2015) and Biomaterials (2014). She earned the Himsley H&A Memorial Prize in 2013 and the Alexander Graham Bell Canada Graduate Scholarship from National Sciences and Engineering Research Council of Canada (NSERC) in 2010 for her research work and academic excellence. Aside from research, Jane was a teaching assistant for five years at the University of Toronto, where she taught undergraduate students about biomaterials and biocompatibility. You can find Jane on Tweeter and LinkedIn.