Teresa Zulueta Coarasa—PhD Defense: The role of cell mechanics in embryonic wound repair: staggered contraction at the leading edge

When:
April 20, 2018 @ 11:00 am – 12:00 pm
2018-04-20T11:00:00-04:00
2018-04-20T12:00:00-04:00
Where:
RS 412
164 College St
Toronto, ON M5S 3E2
Canada

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 Coarsasa

PhD Candidate

Teresa Zulueta Coarasa

Supervisor

Rodrigo Fernandez-Gonzalez, Associate Professor and Canada Research Chair, Quantitative Cell Biology & Morphogenesis

Abstract

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.