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The role of cell mechanics in embryonic wound repair: staggered contraction at the leading edge
This is an open PhD defence in IBBME—all are welcome.
Teresa Zulueta Coarasa
Rodrigo Fernandez-Gonzalez, Associate Professor and Canada Research Chair, Quantitative Cell Biology & Morphogenesis
Epithelia are physical barriers against pathogens. Therefore, the ability of multicellular organisms to self-repair epithelial wounds is critical for survival.
In embryos, wound repair is mediated by the assembly of a contractile supracellular cable at the wound margin composed of filamentous actin and the molecular motor non-muscle myosin II.
It has been proposed that the contraction of the actomyosin cable acts as a “purse-string” to coordinate the movement of cells into the damaged area.
Here, I analyze the physical basis of the “purse string” in Drosophila embryos. Using quantitative image analysis I found that, opposing the idea of a uniform “purse string”, the distribution of cytoskeletal molecules at the wound margin is heterogeneous with areas of high and low protein density. Furthermore, I showed that mutants for the non-receptor tyrosine kinase Abelson (Abl) display a homogeneous distribution of actin at the wound margin that results in slow wound repair.
To investigate the role of actomyosin heterogeneity in wound healing I used biophysical tools to quantify that forces around wounds are also heterogeneous, and patches of the wound edge with heterogeneous actomyosin levels contract faster than homogeneous patches. I developed a mathematical model of wound repair that predicted that actomyosin heterogeneity benefits wound closure if myosin dynamics are directed by tension and strain.
To test this idea in vivo, I inhibited stretch-activated ion channels during wound closure, which resulted in disrupted myosin dynamics and impaired tissue repair.
Together these results suggest that, instead of a “purse-string”, staggered contractility regulates myosin dynamics to coordinate cell movements and to drive fast wound healing.