If you ever get the chance to watch life under a microscope, seize the opportunity. In many ways, microscale life mimics the movies — there are thrilling chases as immune cells hunt down bacterial invaders, a feeling of tragedy as a sick cell bursts and budding romances between cells that crumble in dramatic divorce.
Our bodies are made of trillions of these cells, all of them working in tandem to orchestrate everything that we take for granted, including digestion, thought and healing. For these processes to work, cells must feel their environments and respond appropriately to change. For decades, researchers have studied how cells sense and respond to nearby chemicals, but less is known about how cells respond to physical forces. One University of Iowa laboratory wants to change that.
Edward Sander, an associate professor in biomedical engineering, is using high-powered microscopes — and a bit of “poking” — to understand exactly how our cells feel, sense and respond to these physical forces and how they work together to seal injuries and heal wounds. On the surface, his laboratory is interested in how physical forces inform cell behavior.
“In particular, we are interested in how these forces control wound-healing processes that lead to scarring so that we can devise new ways to reduce scarring and encourage tissue regeneration,” he explained.
The Sander lab accomplishes this by placing keratinocytes, the cells that make up the outermost layer of skin, beneath powerful cameras attached to microscopes. This provides a bird’s-eye view to study how cells respond to all kinds of environmental signals, including nearby wounds. In a recent study, published in the Journal of the Royal Society Interface, Hoda Zarkoob, a graduate student in the Sander laboratory, used a tiny needle to study how keratinocytes move towards a wound to begin the repair process.
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The researchers began by isolating a single keratinocyte cell and placing it on gel-like substances of varying hardness, which mimics human skin tissue. Then, to simulate physical forces exerted by a neighboring cell, they use a tiny needle, controlled by a computer, to gently poke and prod the gel matrix around the cell. The scientists then watch the cells over a 90-minute period, carefully observing how the keratinocytes respond to physical forces and these small, wound-like changes in their environments.
Intriguingly, the team showed that keratinocytes begin to move along the gel by extending long tendrils and pulling themselves along the gel matrix surface. When the researchers poked the gel matrix near the cell, it began to move away from the needle. After about 90 minutes, however, the cell moved back to the “poked” spot on the gel, in much the same way that skin cells migrate to the site of an injury to begin the process of healing and scar formation. This process of keratinocytes moving towards a wound is called re-epithelialization.
“There is a direct relationship between the amount of scar that forms and how fast a wound re-epithelializes,” Professor Sander said of the study’s findings. “The speed of re-epithelialization is dependent on how strong the keratinocytes pull on each other and on the underlying tissue and how soft or stiff the underlying tissue is. If we understand how these physical forces control keratinocyte behavior, then we can figure out new ways to intervene to speed up wound healing.”
By using very simple tools — microscopes, needles and gel — the Sander laboratory is pioneering our understanding of wound healing. As they uncover the principles of scar formation by observing keratinocyte movement, scientists may soon be able to develop therapies, or even engineer living cells directly, to speed up the healing process.