Mechanisms of wound healing

NewsBot · Oct 29, 2013

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Press Release:
Mechanisms of wound healing are clarified in MBL zebrafish study

A crucial component of wound healing in many animals, including humans, is the migration of nearby skin cells toward the center of the wound. These cells fill the wound in and help prevent infection while new skin cells regenerate.

How do these neighboring skin cells know which way to migrate? What directional cues are they receiving from the wound site? A new paper by Mark Messerli and David Graham of the MBL's Eugene Bell Center for Regenerative Biology and Tissue Engineering clarifies the role of calcium signaling in this medically significant communication between skin cells.

Messerli and Graham conducted the study using zebrafish skin cells, which migrate much faster than human cells. "Fish have to heal quickly," Messerli says. "They are surrounded by microbes and fungi in the water. They are constantly losing scales, which generates a wound. So the wound has to be healed in the epidermis first and then a new scale has to be built. Fish skin cells (keratinocytes) migrate five times faster at room temperature than mammalian cells do at 37 degrees C. So it is very easy to track and follow their migratory paths in a short period of time. "

The study brought fresh insights on the role of calcium signaling in inducing cellular organization and directed migration of skin cells. "When we started this study, we were looking at calcium signaling at the single-cell level, which is how it has been looked at for decades. How do single cells see injury?" Messerli says.

To their surprise, by the end of the study they were looking at the calcium signals not just in single cells but in sheets of cells that surround wounds. "The periphery of the wound itself appears to form a graded calcium signal that could direct migration and growth toward the center of the wound. This is what we are looking at now," Messerli says.

The team's approach was to use advanced microscopy to monitor cellular calcium signals and molecular analysis to identify membrane proteins that caused increases in cellular calcium migration. A variety of mechanically activated ion channels were identified in migratory skin cells. TRPV1, the ion channel that is also activated by hot peppers, was found to be necessary for migration.
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NewsBot · Oct 30, 2013

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Press Release:
Mechanisms of wound healing are clarified in MBL zebrafish study
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Epidermal keratinocyte polarity and motility require Ca2+ influx through TRPV1.
Graham DM, Huang L, Robinson KR, and Messerli MA
J Cell Sci. 126: 4602-4613. 2013

Ca2+ has long been known to play an important role in cellular polarity and guidance. We studied the role of Ca2+ signaling during random and directed cell migration to better understand whether Ca2+ directs cell motility from the leading edge and which ion channels are involved in this function by using primary zebrafish keratinocytes. Rapid line-scan and time-lapse imaging of intracellular Ca2+ (Ca2+i) during migration and automated image alignment enabled us to characterize and map the spatiotemporal changes in Ca2+i. We show that asymmetric distributions of lamellipodial Ca2+ sparks are encoded in frequency, not amplitude, and that they correlate with cellular rotation during migration. Directed migration during galvanotaxis increases the frequency of Ca2+ sparks over the entire lamellipod; however, these events do not give rise to asymmetric Ca2+i signals that correlate with turning. We demonstrate that Ca2+-permeable channels within these cells are mechanically activated and include several transient receptor potential family members, including TRPV1. Last, we demonstrate that cell motility and Ca2+i activity are affected by pharmacological agents that target TRPV1, indicating a novel role for this channel during cell migration.
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